A further study of cancer among the Semiconductor (UK) Ltd., Greenock

Health and Safety
Executive
A further study of cancer among the
current and former employees of National
Semiconductor (UK) Ltd., Greenock
20030.01 cover final.indd 1
8/16/10 4:17:07 PM
A further study of cancer among the current and
former employees of National Semiconductor
(UK) Ltd., Greenock
Health and Safety Executive
and
Institute of Occupational Medicine
United Kingdom
Andrew Darnton1, Sam Wilkinson1, Brian Miller2,
Laura MacCalman2, Karen Galea2, Amy Shafrir2,
John Cherrie2, Damien McElvenny3, John Osman1
1
Health and Safety Executive
Epidemiology Unit
Redgrave Court
Merton Road
Bootle
Merseyside L20 7HS
2
Institute of Occupational Medicine
Research Avenue North
Riccarton
Edinburgh EH14 4AP
3
University of Central Lancashire
School of Public Health and Clinical Sciences
Preston
Lancashire PR1 2HE
© Crown copyright 2010
First published 2010
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Information Policy Team, Kew, Richmond, Surrey
TW9 4DU or e-mail: [email protected]
ii
ACKNOWLEDGEMENTS
Current and former management and workers at NSUK Greenock without whom this
investigation could not have been completed, especially Susan Seutter, Bob Steel, and Douglas
Blackwood.
Steering Committee Members, Raymond Agius, Freda Alexander and Oliver Blatchford.
Dr Rod Muir, former chair of the Privacy Advisory Committee, NHS National Services,
Scotland.
Staff at NHS National Services, Scotland, Information and Statistics Division (ISD), especially
Roger Black, David Brewster, Laura Kelso, Susan Frame, Judith Stark, Richard Dobbie, Lesley
Bhatti, David Clark, Douglas Clark, Susan Jensen, and Catherine Storey.
Staff at the National Health Service Central Registers in Dumfries and Southport, especially
Carolyn Macpherson, Muriel Douglas, Gail Turner, Patricia Bell, and Rhona Fraser.
Staff at the Practitioners Services Division in Glasgow, especially Janet Mair, Lesley Taylor and
Wendy Black.
Local GPs and in particular, Dr Jim Ward.
Brenda Bannister (Occupational Health Nurse Practitioner), who carried out interviews on
behalf of IOM.
Many others in HSE, IOM and elsewhere who have provided advice and support.
All those who participated in the study including those contributing to the Historical Hygiene
Assessment.
iii
CONTENTS Executive Summary ........................................................................................ vi
1.
Introduction............................................................................................. 2
1.1
2
3
4
5
Background to the study ............................................................................... 2
Updated Cohort Analysis – Methods and Results .................................. 4
2.1
Methods........................................................................................................... 4
2.2
Statistical methods ........................................................................................ 5
2.3
Results ............................................................................................................ 7
Historical Hygiene Assessment ............................................................. 23
3.1
Introduction .................................................................................................. 23
3.2
Documentary records .................................................................................. 23
3.3
Interviews with long-serving employees ................................................... 23
Case-control and case-only survey – Method and Results.................. 25
4.1
Eligibility of Cases for the Case-control and Case-only studies ............. 25
4.2
Eligibility for Controls.................................................................................. 25
4.3
Sampling methodology for controls........................................................... 25
4.4
The recruitment process ............................................................................. 26
4.5
Interviews...................................................................................................... 29
4.6
Data processing ........................................................................................... 31
4.7
Exposure assessment ................................................................................. 33
4.8
Development of Exposure Matrices ........................................................... 34
4.9
Exposure assignment .................................................................................. 37
4.10
Statistical analysis.................................................................................... 40
4.11
Results....................................................................................................... 41
4.12
False Proxies: Recruitment ..................................................................... 74
Discussion................................................................................................ 80
5.1
Background .................................................................................................. 80
5.2
Findings ........................................................................................................ 81
5.3
Strengths and weakness of the study........................................................ 86
5.4
Interpretation of findings in the context of other studies ........................ 89
6
CONCLUSIONS ........................................................................................ 91
7
References ............................................................................................... 92
iv
Appendix 1 – additional Results Tables and charts.................................... 95
Appendix 2 – Worker Information Leaflet................................................... 115
Appendix 3 – Adjusting the cohort mortality and cancer incidence analysis for deprivation: methodology and comparison of results ......... 117
Appendix 4 – Job Exposure Matrix (JEM) .................................................. 121
Supplementary web material
(Available at UUhttp://www.hse.gov.uk/statistics/nsuk/repapp2010.pdf)
Appendix 5 – Questionnaires and Flashcards Used
Appendix 6 - Letters of invitation to take part in the study
v
EXECUTIVE SUMMARY
INTRODUCTION
This report by a joint research team from Health and Safety Executive (HSE) and the Institute of
Occupational Medicine (IOM) describes the results of a study carried out in response to the
findings of an earlier investigation into concerns about cancer at National Semiconductor (UK)
Ltd (NSUK). That investigation could not exclude the possibility that work at NSUK may have
contributed to the higher than expected incidence of certain cancers, and particularly lung
cancer, in the workforce. It recommended further research to follow up those findings and
prompted the investigation reported here.
The aim of this study was to assess the whether workplace exposures contributed to any
increased risk of these cancers by carrying out:
1. an update of the original cohort analysis of overall mortality and cancer incidence
among this workforce;
2. a plant-based case-control study of lung cancer and breast cancer in which the work and
lifestyle histories of cases and a sample of NSUK workers without these cancers would
be compared;
3. an examination of the work and lifestyle histories of the smaller number of cases of
female stomach and male brain cancer.
The protocol for the study was approved by the appropriate local NHS Research Ethics
Committee and Research and Development function, and by the Privacy Advisory Committee
for the NHS National Services, Scotland, Information and Statistics Division (ISD), and General
Register Office for Scotland (GROS).
During the course of the study the protocol was amended to restrict the lung cancer analysis to
an examination of the work and lifestyle histories of cases only rather than a full case-control
analysis because of the low response rate amongst the cases. This change was agreed with the
local research ethics committee and the NSUK workforce was informed.
METHODS
The updated cohort analysis was carried out using same methodology as in the original study.
Deaths and cancer registrations among the workforce were obtained in order to calculate
Standardised Mortality Ratios (SMRs) and Standardised Cancer Registration Ratios (SRRs) for
a predefined set of disease groups using reference rates based on Scottish national mortality and
cancer registration data. We examined the same disease groups as in the original analysis with
the addition of brain, central nervous system and ovarian cancer. Since NSUK workers were
drawn from an area with higher than average levels of deprivation, we adjusted SMRs and
SRRs to allow for associations between these diseases and deprivation.
An Historical Hygiene Assessment (HHA) was undertaken to gather information about
processes, working practices and working conditions at the NSUK plant since it opened.
Documentary evidence from NSUK and HSE inspections was reviewed and supplemented by
information from interviews of long serving NSUK employees nominated by NSUK and Phase
Two, a local support group for workers at the plant. This assessment was used to develop a job
exposure matrix that linked jobs done at NSUK to specific hazards that might be encountered in
that job.
Cases of female breast, lung and stomach cancer, male brain cancer, and a random sample of
control subjects individually age-matched to the breast cancer cases, were identified from within
vi
the study dataset. Invitations to participate in the study were sent to individuals through their
GPs. We identified suitable proxy respondents for deceased cases and controls by contacting
relatives identified from death certificates. Face-to-face interviews of subjects and proxies were
carried out by a dedicated nurse, blinded to case-control status, using structured questionnaires
to obtain job and lifestyle histories. Non-occupational factors considered were alcohol
consumption, smoking, type of housing, attained education level, and family history of breast
cancer.
The job-exposure matrix included general groups of key substances (solvents, acids, and gases)
as well as specific known and suspected carcinogens. Exposures were assigned to cases and
controls via the particular processes recorded in individual work histories. Exposures in jobs
outside NSUK were assigned using a published Job Exposure Database (FINJEM) and exposure
to shift work both at NSUK and elsewhere was also assessed. Duration of exposure to each
hazard was estimated by the number of years worked on processes where there was potential
exposure.
Evidence for associations between breast cancer and exposure to NSUK and other hazards was
assessed by comparing the likelihood of exposure among cases relative to that among control
subjects, as expressed in the form of Odds Ratios (ORs) calculated using standard conditional
logistic regression methods. The response rate for lung cases meant that a similar analysis was
not feasible.
MAIN FINDINGS AND CONCLUSIONS
The updated study gives us a stronger basis of evidence for assessing whether work at NSUK
contributed to the adverse health of the workforce than available from the original study, though
it is never possible with this type of research to completely rule out such an effect. The IBM
studies also provide important new evidence which we have taken into account in reaching our
conclusions.
The overall pattern of mortality and cancer incidence was similar in the updated study to that
seen originally, with a substantial deficit of deaths from all causes among men, and a less
substantial deficit among women, compatible, at least in part, with a healthy worker effect.
Total numbers of registrations (all kinds of cancer combined) were in line with expectation for
both men and women.
The cohort study findings for female lung cancer now appear unremarkable in the sense of
epidemiological evidence of an association: in particular there was no longer any excess of
registrations with time since first employment restricted to 10 years or more, either overall or
among cohort subgroups. We have not been able to explore the findings further by means of a
nested case-control study and therefore have not been able to say whether any of the known
lung carcinogens or other substances in use at NSUK might or might not have contributed to the
development of any of the cases. The two industry wide inspection initiatives undertaken by
HSE in 2002 and 2009 do, however, draw attention to the potential for arsenic exposure in the
semiconductor chip manufacturing industry, and arsenic is an established cause of lung cancer.
Taking account of all the information, including that from the IBM study, we have concluded
that there is no convincing evidence of an occupational risk of lung cancer.
In the updated cohort analysis there were 37.6 breast cancer registrations expected and 46
observed; this difference was not statistically significant. None of the analyses with time since
first employment restricted to 10 years or more showed statistically significantly more cases
than expected and there was no trend with duration of employment.
vii
The breast cancer case-control study was based on a small number of cases (21 out of 40 (53%)
cases contributed information of which 20 were included in the overall analysis and 13 in the
analysis excluding proxy respondents) and so the results must be interpreted with caution.
Exposure to the general category of gases and three of the specific hazards (arsenic and its
compounds, antimony trioxide and sulphuric acid mist) was associated with an increased
likelihood of breast cancer in some of the analyses, but not all. Those categorised as exposed to
one of these agents tended to also be categorised as exposed to all the others, making it difficult
to distinguish which exposures might point towards any real effect if any such effect existed.
There is a lack of supporting evidence in the scientific literature of associations with breast
cancer risk for any of the specific substances included in the gases category, nor is there any for
arsenic, antimony trioxide or sulphuric acid mist (though antimony has not been studied
extensively). In summary, the case-control study for breast cancer has not revealed any
associations that could confidently be attributed to exposures during work at NSUK.
Overall, the evidence for an occupational risk of breast cancer from our studies remains as weak
as before. The evidence now available from the study at IBM is not supportive of an
occupational risk.
The updated cohort study findings in respect of female stomach cancer and male brain cancer,
together with the detailed investigation of two of the cases of stomach cancer and all four of the
cases of brain cancer, did not provide any additional evidence to support a possibility that work
at NSUK is likely to have led to an increased risk of these cancers. Nor were the case only
studies able to help in excluding the possibility of a workplace cause by showing that cases of
either cancer each had different exposures. There were no positive findings for stomach cancer
in the IBM study. An association between process equipment maintenance and brain cancer
mortality was identified for one site in the IBM study, but only one case of brain cancer in our
study was recorded as having a maintenance role.
In the cohort analysis, there were 11 observed cases of colo-rectal cancer and 5.9 expected; this
difference was not statistically significant. In some subgroup analyses with time since first
employment restricted to 10 years or more, results appeared statistically significant. However,
other features of the results, such as a lack of trend with duration of employment, tend to argue
against these findings as suggesting that work at NSUK has led to an increased risk of these
cancers. The IBM study findings are consistent with this view.
OVERALL CONCLUSIONS
Our new research does not support the earlier concerns about a link between working at NSUK
and developing cancer, especially when taking account of new information about cancer at two
IBM semiconductor factories in America.
The evidence from this most recent study does not prompt HSE to recommend any further
epidemiological research in the way the evidence from previous study did. In any case there is
no such research that could be done within the NSUK setting at this stage.
The Historical Hygiene Assessment that was undertaken as part of this study should provide a
valuable resource for the local interpretation of any further evidence that may emerge about
cancer in the semiconductor industry as a consequence of studies now underway or undertaken
in the future.
viii
1. INTRODUCTION 1.1
BACKGROUND TO THE STUDY
In 1998 the Health and Safety Executive (HSE) began work on a study to investigate rates of
cancer incidence and mortality among current and former workers at the National
Semiconductor (UK) Ltd (NSUK) manufacturing facility at Greenock. The study was prompted
by concerns expressed at the time about a possible increase in risk of cancer for these workers.
It aimed to establish if there was any objective evidence of excess cancer occurrence in the
workforce and, if so, was there any evidence to suggest that this was related to work at the
facility.
The scope of the study was limited to establishing levels of cancer incidence and mortality in
the workforce; comparing with expected levels for a population with the same age, sex and
social and economic profile; and relating this to readily available information about different
work practices at the factory such as work in clean rooms (fabs). The intention was to then
consider the need for more extensive investigation based on these findings.
The study 1,4 found that, after accounting for local social and economic factors, overall levels of
mortality among women were below expected and those among men were substantially below
expected. Total cancer registrations were close to expected levels for both men and women.
However, although based on a small number of cases, some (though not all) of the results of
more detailed analyses for some specific kinds of cancer did indicate to HSE a need for further
investigation of the possible role of work at NSUK in causing some of the cases.
The most noteworthy finding was the observation of 11 female cases of lung cancer compared
with 4 expected (after allowing for factors associated with deprivation such as smoking). There
were also 3 cases of female stomach cancer and although this number is small, it was more than
4 times higher than the calculated expected number of cases of this rare cancer (less than 1
case).
There were also 20 cases of female breast cancer compared with 15 expected, and 4 cases of
male brain cancer compared with less than 1 expected. Since the breast cancer finding was not
statistically significant, and given that brain cancer had not been identified a priori as a cancer
of concern, these findings were considered less suggestive of a workplace explanation.
The findings led to three recommendations for further study:
1) An update of the original cohort analysis should be carried out at an appropriate point in
the future when the typical elapsed time since individuals started work at NSUK would
be longer and allow a better assessment of the overall cancer experience.
2) An NSUK plant based case-control study should be established to compare the history
of exposure to carcinogens among those with the particular kinds of cancer of concern
(primarily stomach and lung cancer, but also breast and brain cancer) with exposure
histories of comparable individuals who have not developed these cancers.
3) An industry-wide study within the UK, sponsored by the industry and along the lines of
the original HSE study should be carried out so that the overall cancer experience of all
workers in the industry can be characterised.
2
This report by a joint research team from HSE and IOM describes the results of work
undertaken since the original HSE study in respect of the first two of these recommendations.
HSE, together with the then Department for Trade and Industry, funded an investigation2
confirming the feasibility of an industry-wide study but to date the UK industry has not initiated
such a study, although an industry wide study funded by the Semiconductor Industry
Association is underway in the USA.
1.2
DEVELOPMENT OF THE STUDY PROTOCOL AND ETHICAL CLEARANCE
An initial protocol was developed such that the study could address local community factors
that might affect the health (and in particular the mortality and cancer incidence) of the
workforce. This protocol was shared with NSUK management who in turn sought the advice of
a number of international experts.
The HSE/IOM research team met with NSUK and its expert advisers to discuss this protocol
and the outcome was a decision to focus more specifically on possible workplace explanations
for the excesses seen in the original study, and to include potential confounding factors such as
smoking and other aspects of lifestyle, and previous occupation in the data collected so that it
was available for analysis. A further protocol was then developed which built on the established
epidemiological technique of a nested case-control study as the means for addressing the earlier
findings for lung and breast cancer in females. Because of the particularly small numbers of
cases of female stomach and male brain cancer it was agreed that case-control methodology was
inappropriate but that it might be possible to throw some light on any possible relationship
between these cancers and work factors by examining the work histories of the cases together
with any other relevant lifestyle and work history information.
The protocol was discussed with an independent Scientific Steering Committee whose members
were the same as those who advised on the initial study except that Dr Oliver Blatchford
replaced Dr Louis Reay as a public health representative.
The final study protocol3 and associated documentation were approved by the appropriate local
NHS Research Ethics Committee and by the Privacy Advisory Committee for the NHS National
Services, Scotland, Information and Statistics Division (ISD), and General Register Office for
Scotland (GROS). Four subsequent Substantial Amendments were submitted to the Research
Ethics Committee and approved. The changes associated with these amendments are described
in relevant sections of this report.
The final protocol was also shared with the (then) current workforce and with Phase Two, a
support group for workers at the NSUK Greenock plant.
3
2
UPDATED COHORT ANALYSIS – METHODS AND RESULTS
2.1
METHODS
2.1.1
Definition and construction of the cohort
Definition and construction of the cohort is described in detail in the research report for the
original study1,4. Briefly, a range of data sources at NSUK were used to establish a list of
individuals who the company could confirm had worked at the Greenock plant on or before 30
April 1999. Following a number of exercises to check the completeness and accuracy of the data
provided, a final dataset containing the name, sex, date of birth, employment dates and the last
known address of each individual, as well as an indication of whether they had ever worked in
clean room areas (fabs), was produced. Our updated analysis is based on the same cohort of
4388 workers confirmed as having worked at the plant and who were also traced by the GROS.
No new information about the employment history of existing cohort members has been added
for the purpose of this updated analysis, and no additional individuals have been included.
2.1.2
Case ascertainment
All 4388 individuals traced by the General Register Office for Scotland (GROS) as part of the
original study had been flagged in the National Health Service Central Register (NHSCR) for
notification of subsequent death and cancer registrations, embarkations and name changes. New
notifications were added to the study data file on a regular basis (approximately quarterly) by
the HSE study team. In 2007 an electronic file was obtained containing details of all NSUK
cohort members flagged on the GROS database in order to check the completeness of death and
cancer registration information input since the original analysis was carried out.
As in the original analysis, all individuals on the cohort file were also checked against the
Scottish Health Service Information and Statistics Division (ISD) cancer registration database
via a probability matching algorithm in order verify the completeness of the cancer registration
notifications from GROS. This data linkage exercise was carried out in April/May 2007 prior to
recruitment of subjects for the case-control study in order to ensure that all cases known to ISD
by that point could be included. A further data linkage exercise was carried out in September
2009 prior to carrying out the updated cohort analysis in order to ensure complete ascertainment
of cancers before the cut off date for follow-up (31 December 2006).
2.1.3
Disease groups
The basis for choice of disease groups in the original study is described in the associated
research report1. The same set of priority disease groups and cancer sites was used in the
updated analysis, with the addition of brain cancer, brain cancer combined with central nervous
system cancers, and ovarian cancer. These three groups were added in the light of the findings
of the original study and a study of IBM workers in the USA5,6.
4
2.2
STATISTICAL METHODS
2.2.1 Calculation of Standardised Mortality Ratios (SMRs) and Standardised
Registration Ratios (SRRs)
Mortality analyses were based on the underlying cause of death recorded on death certificates,
as coded to the revision of the International Classification of Diseases (ICD) in use at the time
of death: revision 8 (ICD8) for deaths occurring before 1979, revision 9 (ICD9) for deaths from
1979-1999 and revision 10 (ICD10) for deaths from 2000 onwards. Analyses of cancer
registrations were based on events supplied by ISD with cancer sites coded according to ICD9
for cancers registered before 1997, and ICD10 for those from 1997.
Assessment of mortality and cancer incidence among the NSUK cohort in relation to numbers
of expected deaths and cancer registrations was made by calculating Standardised Mortality
Ratios (SMRs) and Standardised Registration Ratios (SRRs) for each disease group. Expected
deaths and cancer registrations were calculated using Scottish national death and cancer rates
with adjustment for deprivation to ensure they were representative of local rates most relevant to
former NSUK employees. These rates were derived from the same source data that provide the
basis for numbers of deaths and cancer registrations among cohort members in order to avoid
numerator-denominator bias.
Follow-up in the mortality analysis was counted from the date of first employment at NSUK
until the latest year for which complete death information was available (31 December 2007),
the date of death, or the date of embarkation, whichever was earliest. Similarly, follow-up in the
cancer registration analysis was counted from the date of first employment until the latest year
for which cancer registration information was available (31 December 2006), the date of death,
or date of embarkation, whichever was earliest. In the cancer registration analysis, individuals
were assumed to continue to be at risk beyond the occurrence of any particular cancer
registration they had, since multiple registrations may be recorded for individuals within the
cancer registration system.
Scottish death and population data for 1970-2007 obtained from GROS were used to calculate
death rates by sex, five-year age group, and calendar time period for the disease groups in the
analysis. Scottish cancer registration data for 1970-2006 obtained from ISD were used to
calculate cancer registration rates in the same format for those disease groups appropriate for the
cancer registration analysis. The resulting mortality and cancer registration rates were checked
against published data where available7,8.
Each SMR and SRR is presented with its associated 95% confidence interval, calculated by
assuming that deaths and cancer registrations are independent events that occur following a
Poisson distribution. The confidence intervals give an indication of the amount of statistical
uncertainty. The smaller the number of deaths or cancers on which an SMR or SRR is based, the
wider the associated confidence interval.
While the SMR or SRR itself represents the most likely value of the ratio of observed deaths (or
cancers) to expected numbers, the confidence interval provides a guide as to the range of
plausible values that are consistent statistically with the observed data. Values of the SMR or
SRR beyond the upper and lower bounds of the confidence limits are statistically much less
plausible than those close to the centre of the range. An SMR or SRR is said to be statistically
significant if the value of 100 (which indicates that same number of observed deaths or cancers
as expected) lies outside the confidence interval. In keeping with convention, when describing
the results of our analyses we have often referred to excesses or deficits of deaths and cancer
5
registrations where SMRs or SRRs were statistically significantly greater than, or less than, 100
respectively.
Statistical analyses were carried out using SPSS v159, STATA v810 and OCMAP-PLUS v411.
2.2.2
Adjustment for deprivation
The deprivation adjustment was carried out as follows. Post codes for workers in employment at
NSUK on 30 April 1999 were used to derive the distribution according to quintiles of the
Carstairs index12 separately for males and females. These were assumed to be representative of
the deprivation distributions of all men and women in the NSUK cohort. Scottish mortality and
cancer registration data for three separate time periods, broken down by Carstairs quintile for
each of the disease groups, were then used in conjunction with the estimated NSUK distribution
to weight the Scottish comparison rates used in the SMR and SRR analyses. Data for 1979-83
were used to weight comparison rates prior to 1985, data for 1989-93 to weight rates for 1985­
1994, and data for 1997-2004 to weight rates from 1995 onwards. Further details are given in
Appendix 3.
Data were not available according to the Scottish Index of Multiple Deprivation (SIMD) for
deaths and cancer registrations occurring prior to 1997. We were thus unable to adjust earlier
rates using the appropriate earlier national data for this new index of deprivation. However, we
calculated an alternative set of adjusted mortality and cancer registration rates using Scottish
data for 1997-2004 by SIMD quintile to weight rates for all time periods from 1970. SMRs and
SRRs calculated using these alternative rates were compared with those based on Carstairs
adjusted rates to check the potential impact on the analysis. We also calculated SMRs and SRRs
using rates adjusted under the assumption that all individuals within the cohort were in the
highest Carstairs quintile in order to assess the maximum impact of deprivation on the results
using this methodology.
2.2.3
Analysis of cohort subgroups
Since information on exposures was not available in the cohort analysis we were unable to
directly allow for the effects of latency (the delay between exposure to a disease-causing agent
and the appearance of manifestation of the disease). Instead we carried out analyses of mortality
and cancer incidence in relation to the length of time since the start of employment at the plant.
The cut-off for the categories in these analyses was set at 10 years, which is likely to be the
minimum latency period for most solid tumours. Any excess of deaths or registrations from
such cancers in the subgroup with less than 10 years since first employment is therefore less
likely to be suggestive of cause related to work at the plant.
More detailed analysis of cohort subgroups considered the following:

age (<50 years or ≥50 years),

date first employed at the plant (before 1982 and 1982 onwards),
plant work area (fab or non-fab areas)

duration of employment (<1 year, 1 to 4 years, 5 to 9 years or ≥10 years)

The categories for age were originally chosen to have approximately equal expected numbers of
all malignant neoplasm cancer registrations. Similarly, in the original analysis, 1 January 1982
was chosen as the cut-off to divide the cohort into two categories based on date first employed
at NSUK so that each had approximately equal numbers of expected all malignant neoplasm
registrations. We used this same cut-off in the updated analysis for consistency with the earlier
6
one even though the additional follow-up suggested a later date. The assignment of individuals
to plant work area is described in detail in Appendix 5 of the original report1. This provides a
crude marker of those who spent at least a part of their employment time within fab areas and
therefore having potential exposure to a wide range of agents characteristic of semiconductor
fabrication.
Duration of employment was not included in the original analysis because of more limited
follow-up (mean length of follow-up was only 12.5 years in the original mortality analysis). In
this analysis we used 4 categories which broadly equate to quartiles of the distribution of
duration of employment for the whole cohort. We carried out significance tests for
heterogeneity in SRRs for these categories as well as tests for trend in SRRs with increasing
duration of employment. Since no new information about the employment history of existing
cohort members was obtained, any employment beyond 30 April 1999 could not included in
these analyses, and as a consequence duration will be underestimated in some individuals.
2.3
2.3.1
RESULTS
Descriptive statistics
The results of the original tracing exercise by GROS have been described in detail in the
original report1,4 Briefly, after data reconciliation the final cohort consisted of 4950 individuals,
and their details were sent for tracing. Of these, 4547 were confirmed by NSUK during the data
reconciliation process as having worked at the plant. Of these confirmed NSUK workers, 4388
(96.5%) were traced, the majority in Scotland (4067) with smaller numbers in England/Wales
(318) and Northern Ireland (3). Of the 403 individuals not confirmed as having worked at
NSUK Greenock, 257 (63.7%) were traced. All 403 of these unconfirmed Greenock workers
were excluded from analyses.
Additional follow-up time in the updated analyses (7 years for the mortality; 8 years for cancer
incidence) led to a substantial increase in the number of person-years of observation, as shown
in Table 2.1 below. Women accrued more observation time than men. The mean length of
follow-up was 19.3 years in the updated analysis compared with 12.5 in the original analysis.
Table 2.1 Person years of observation in the original and updated study, by sex
(End of follow-up)
Mortality analysis
Original analysis
(31 December 2000)
Updated analysis
(31 December 2007)
Cancer incidence analysis
Original analysis
(31 December 1998)
Updated analysis
(31 December 2006)
Male
Female
Total
24,842
30,171
55,014
39,294
45,439
84,733
20,558
25,343
45,901
37,243
43,213
80,456
The distribution of cohort members by decade of birth is shown in Table 2.2 below.
7
Table 2.2 Distribution of cohort by decade of birth and sex
Male
(%)
Female
(%)
Total
(%)
1920-29
10
0.5
11
0.5
21
0.5
1930-39
47
2.2
100
4.4
147
3.4
1940-49
165
7.8
266
11.8
431
9.8
1950-59
454
21.4
574
25.4
1028
23.4
1960-69
966
45.4
971
42.9
1937
44.1
1970-79
466
21.9
340
15.0
806
18.4
1980-89
18
2126
0.8
(100.0)
0
2262
0.0
(100.0)
18
4388
0.4
(100.0)
Birth decade
Total
The distribution of the vital and cancer status of the 4388 individuals included in either of the
cohort analyses is shown in Table 2.3 below. Two individuals excluded from the original
cancer registration analysis because they started work after the end 1998 were included in the
updated analysis.
By the end of 2007, the total number of deaths among the cohort had about doubled to 145
(3.3%). By the end of 2006, the total number of individuals with at least one cancer registration
had almost doubled to 251.
Table 2.3 Vital and cancer status of cohort members at end of follow up in the original
and updated cohort analyses, by sex
Vital status at 31/12/2000
Vital status at 31/12/2007
Male
Female
Total
Male
Female
Total
Alive
2088
2211
4299
2038
2152
4190
Deceased
27
44
71
61
84
145
Embarkations#
TOTAL
11
7
18
27
26
53
2126
2262
4388
2126
2262
4388
Cancer status at 31/12/1998
Male
Female
Total
2100
2158
4258
25
98
123
No cancer
1 relevant* cancer registration
More than 1 relevant* cancer
0
2
2
registration
TOTAL
2125
2258
4383
*Cancers occurring after the date first employed at NSUK Greenock
#
Individuals who have left the NHSCR system
8
Cancer status at 31/12/2006
Male
Female
Total
2062
2072
4134
63
175
238
1
12
13
2126
2259
4385
2.3.2
Overall mortality and cancer incidence
Overall observed numbers of deaths and cancer registrations are shown in Table 2.4. Numbers
of deaths and Standardised Mortality Ratios (SMRs), with and without adjustment for
deprivation, are shown in Table 2.5 and Table 2.6. Similarly, numbers of cancer registrations
and Standardised Registration Ratios (SRRs) are shown in Table 2.7 and Table 2.8 All results
described below are with adjustment for deprivation unless otherwise stated.
There was a substantial deficit of male deaths overall with 61 deaths observed versus 137
expected (SMR 44.5, 95% CI 34.1-57.2). This deficit persists with time since start of
employment restricted to 10 years or more. Deaths from all malignant neoplasms among men
showed a deficit below expected levels of a similar magnitude (12 deaths observed, 27.6
expected, SMR 43.4, 95% CI 22.5-75.9). The results for the other major disease groups
considered showed that there were fewer male deaths than expected due to diseases of the
respiratory system (1 death observed, 7.4 expected, SMR 13.6, 95% CI 0.3-75.7). There was
also a suggestion of fewer male deaths than expected from diseases of the circulatory system
(25 deaths observed, 35.8 expected, SMR 69.8, 95% CI 45.1-103), though this result was not
statistically significant. For the specific cancer site groups considered there were fewer male
deaths than expected among males due to lung cancer (2 deaths observed, 8 expected, SMR
24.9, 95% CI 3-90). The 3 brain cancer deaths among men versus 1.6 expected does not
represent a statistically significant excess (SMR 185, 95% CI 38.3-542).
There were 84 deaths overall among women versus 116 expected and this also represents a
substantial deficit (SMR 72.8, 95% CI 58.0-90.1), though not as large as that for men. This
deficit also persists with time since start of employment restricted to 10 years or more.
However, female mortality from all malignant neoplasms was consistent with expectation (SMR
101, 95% CI 72.6-136.2). There were fewer female deaths than expected due to diseases of the
circulatory system (13 deaths observed, 26.9 expected, SMR 48.4, 95% CI 25.8-82.8) but in
contrast to males, there was no evidence of a deficit of deaths due to diseases of the respiratory
system (6 deaths observed, 9.1 expected, SMR 66.3, 95% CI 24.3-144). Numbers of female
stomach cancer deaths were higher than expected, though not statistically significantly so (4
observed, 1.1 expected, SMR 362, 95% CI 98.6-926); this was also the case for female lung
cancer deaths (15 observed, 9.6 expected, SMR 157, 95% CI 87.6-258). The number of deaths
from female breast cancer was consistent with expectation (10 deaths observed, 9.6 expected,
SMR 104, 95% CI 49.9-192).
In contrast to the mortality results, total numbers of registrations for all malignant neoplasms
among men were consistent with expectation, both overall (62 registrations, 68.7 expected, SRR
90.2, 95% CI 69.1-116) and with time since start of employment restricted to 10 years or more
(Table 2.9). None of the specific cancer site groups identified for study at the outset showed
observed numbers of cancer registrations among men that were statistically different to
expectation. There were 4 male lung cancer registrations versus 8.9 expected (SRR 45.1, 95%
CI 12.3-116) and 4 male brain cancer registrations versus 1.9 expected (SRR 209, 95% CI 57­
535).
The disease group Cancers of the digestive organs and peritoneum was not identified for
investigation at the outset. However, in view of the fact that 14 out of the 15 registrations
among men for these cancers occurred more than 10 years after the start of employment at the
plant, further analyses were carried out focussing on those specific cancer sites within this
category that could plausibly have the same aetiology, such as colo-rectal cancer. These
analyses were not adjusted for deprivation since the appropriate data had not been obtained at
the time of analysis, and we noted that the adjustment had a relatively small impact on the
9
results for cancers of the digestive organs and peritoneum overall. Of the 15 registrations for
cancer of the digestive organs and peritoneum among men, 11 were for colo-rectal cancer
versus 5.9 expected (unadjusted SRR 186, 95% CI 93-333).
Total numbers of registrations for all malignant neoplasms among women were consistent with
expectation, both overall (122 registrations, 119 expected, SRR 102, 95% CI 84.9-122) and with
time since start of employment restricted to 10 years or more (Table 2.10). The number of
female stomach cancer registrations was higher than expected, a result of borderline statistical
significance based on 5 registrations, of which 2 were for the same individual (SRR 312, 95%
CI 101-729). The 16 registrations of female lung cancer do not represent a statistically
significant excess (11.1 expected, SRR 144, 95% CI 82.3-234). The number of registrations of
female colo-rectal cancer were in line with expectation (6 registrations, 6.8 expected, SRR 87.8,
95% CI 32.2-191).
2.3.3
Detailed analyses
More detailed results for cancer registrations are presented for those cancer sites for which
detailed results were presented in the original analysis (female lung cancer, stomach cancer and
breast cancer) and for any additional sites where we considered some discussion as to whether
the updated results might be suggestive of an occupational association was warranted (male
colo-rectal cancer). These results are shown in Table 2.11 to Table 2.18.
Of the 16 female lung cancer registrations, 7 occurred within 10 years from the start of
employment, 7 occurred between 10 and 20 years, and 2 occurred after at least 20 years. Age at
diagnosis ranged from 44 to 61 years. Three of the women with lung cancer had had previous
cancer registrations for cancers other than lung cancer after starting work at the plant. All 16
women had died prior to the end of 2006. For 14, lung cancer was recorded as the underlying
cause of death and they were included in the mortality analysis.
There was no excess of female lung cancer registrations when time since start of employment
was restricted to 10 year or more (9 registrations, 8.8 expected, SRR 102, 95% CI 46.5-193)
although there was a statistically significant excess when time since start of employment was
restricted to less than 10 years (7 registrations, 2.3 expected, SRR 309, 95% CI 124-637).
Statistically significant excesses seen among the subgroup analyses were seen only when time
since start of employment was restricted to less than 10 years. There was no evidence of any
difference in the frequency of lung cancer registrations relative to expected levels within
different categories of duration of employment.
The 5 female stomach cancer registrations occurred among 4 women. Of the five registrations, 3
occurred within 10 years from the start of employment, and 2 occurred between 10 and 20
years. All four women were aged 50 years or less at first diagnosis and all had died before the
end of 2006.
All five female stomach cancer registrations were among women who had worked at the plant
for more than 5 years, and 4 of these occurred before age 50 years. There were 2 registrations
among women first employed before 1982, and three among those who had worked in fab areas.
There were 46 female breast cancer registrations among 41 individual women. Of the 46
registrations, 17 occurred within 10 years from the start of employment, 16 occurred between
10 and 20 years, and 13 after at least 20 years. Age at diagnosis ranged from 28 to 67 years.
Three women had more than one breast cancer registration since working at the plant. Eleven of
10
the 41 women had died before the end of 2006; the underlying cause of death was recorded as
breast cancer in 9 cases.
Analysis of cohort subgroups revealed two instances where the number of breast cancer
registrations was statistically significantly higher than expected: women aged 50 years or more
and women first employed in 1982 or later. However, in both cases no excess was seen with
time since start of employment restricted to 10 years or more. There were 13 breast cancer
registrations among those who had worked at the plant for less than 1 year, about twice the
number expected in this category (SRR 203, 95% CI 108-347).
Of the 4 male brain cancers, 3 occurred within 10 years since the start of employment, and 1
occurred between 10 and 20 years. All four cases had worked at the plant for between 1 and 10
years and three occurred before age 50 years. Three of the men were first employed after 1982,
and none were recorded as having worked in fab areas.
Among men, 14 of the 15 cancers of the digestive organs and peritoneum occurred more than 10
years from the start of employment. Of these 15 cancers, 7 were colon cancers, 4 were rectal
cancers, 2 were liver cancers, 1 was a stomach cancer and 1 was a peritoneal cancer. Of the 11
cases of colorectal cancer among men, 10 occurred after 10 years from the start of employment
versus 4.3 expected (unadjusted SRR 235, 95% CI 113-433). However, among the subgroup
analyses, the only significant excess was for men aged more than 50 years (9 registrations, SRR
238, 95% CI 109-452). Six of the 11 cases were among men first employed before 1982, and 4
were among men classified as having worked in fab areas. There was no evidence of any
difference in the frequency of colo-rectal cancer registrations relative to expected levels within
different categories of duration of employment.
11
Table 2.4 Number of deaths and cancer registrations by disease group and sex
Disease group
Male
Deaths
Female
Total
All causes
61
84
145
-
-
-
All malignant neoplasms
Malignant neoplasms of the lip, oral
cavity and pharynx
Malignant neoplasms of digestive
organs and peritoneum
Malignant neoplasms of the
stomach
Malignant neoplasms of respiratory
and intrathoracic organs
Malignant neoplasms of trachea,
bronchus and lung
Malignant neoplasm of the pleura
Malignant neoplasms of other
genitourinary organs
Malignant melanoma of the skin
Other malignant neoplasm of the
skin
Malignant neoplasm of the breast
12
42
54
62
122
184
1
0
1
2
3
5
4
8
12
15
15
30
0
4
4
1
5
6
2
15
17
7
16
23
2
15
17
4
16
20
0
0
0
0
0
0
0
2
2
11
11
22
0
1
1
3
5
8
1
0
1
11
17
28
-
10
10
-
46
46
Malignant neoplasm of the uterus
0
0
0
0
2
2
Malignant neoplasm of the ovary
Malignant neoplasm of the thyroid
gland
Malignant neoplasms of the
lymphatic and haematopoietic tissue
Multiple myeloma
-
1
1
-
4
4
0
0
0
0
0
0
1
2
3
6
4
10
0
0
0
2
0
2
0
1
1
0
1
1
0
1
1
0
1
1
3
0
3
4
0
4
3
0
3
4
0
4
Benign neoplasms
0
0
0
0
2
2
In situ neoplasms
Neoplasms of uncertain or
unspecified behaviour
All neoplasms
Diseases of the blood and blood
forming organs
Diseases of the circulatory system
0
0
0
0
75
75
0
0
0
3
2
5
12
42
54
65
201
266
0
0
0
-
-
-
25
13
38
-
-
-
1
6
7
-
-
-
0
1
1
-
-
-
Leukaemia
Leukaemia, except chronic
lymphatic leukaemia
Malignant neoplasm of the brain
and central nervous system
Malignant neoplasm of the brain
Diseases of the respiratory system
Diseases of the genitourinary
system
12
Cancer registrations
Male Female
Total
Table 2.5 Male mortality by disease group: numbers of deaths and SMRs with and without adjustment for deprivation
Observed
Unadjusted for deprivation
Adjusted for deprivation
Disease group
deaths
Expected
SMR (95% CI)
Expected SMR
(95% CI)
All causes
61
116
52.4 (40.1, 67.3)
137
44.5 (34.1, 57.2)
All malignant neoplasms
12
25.2
47.6 (24.6, 83.1)
27.6
43.4 (22.5, 75.9)
1
0.9
..
1.1
..
Malignant neoplasms of the lip, oral cavity and pharynx
4
7.5
53.1 (14.5, 136)
8.2
49 (13.4, 126)
Malignant neoplasms of digestive organs and peritoneum
0
1.2
..
1.4
..
Malignant neoplasms of the stomach
Malignant neoplasms of respiratory and intrathoracic
2
7.3
27.6 (3.3, 99.6)
8.6
23.4 (2.8, 84.4)
organs
Malignant neoplasms of trachea, bronchus and lung
2
6.8
29.4 (3.6, 106)
8
24.9 (3, 90)
Malignant neoplasm of the pleura
0
0.1
..
0.1
..
Malignant neoplasms of other genitourinary organs
0
2.5
- (0, 149)
2.6
- (0, 143)
Malignant melanoma of the skin
0
0.6
..
0.6
..
Other malignant neoplasm of the skin
1
0.1
..
0.1
..
Malignant neoplasm of the thyroid gland
0
0.1
..
0
..
Malignant neoplasms of the lymphatic and
1
2.3
43.2 (1.1, 241)
2.3
43.5 (1.1, 243)
haematopoietic tissue
0.3
..
0.3
..
Multiple myeloma
0
0.8
..
0.8
..
Leukaemia
0
0.7
..
0.7
..
Leukaemia, except chronic lymphatic leukaemia
0
Malignant neoplasm of the brain and central nervous
3
1.6
182 (37.6, 532)
1.6
185 (38.3, 542)
system
189 (39, 552)
1.6
186 (38.5, 545)
1.6
Malignant neoplasm of the brain
3
0
0.1
..
..
Benign neoplasms
Neoplasms of uncertain or unspecified behaviour
0
0.2
..
..
All neoplasms
12
25.5
47 (24.3, 82.1)
27.9
42.9 (22.2, 75)
Diseases of the blood and blood forming organs
0
0.2
..
0.2
..
Diseases of the circulatory system
25
31
80.8 (52.3, 119)
35.8
69.8 (45.1, 103)
Diseases of the respiratory system
1
5.9
16.9 (0.4, 94.3)
7.4
13.6 (0.3, 75.7)
Diseases of the genitourinary system
0
0.6
..
0.8
..
.. SMRs not calculated where both the observed and expected deaths <2
13
Table 2.6 Female mortality by disease group: numbers of deaths and SMRs with and without adjustment for deprivation
Observed Unadjusted for deprivation
Adjusted for deprivation Disease group
deaths
Expected SMR (95% CI)
Expected SMR (95% CI) All causes
84 92.4 90.9 (72.5, 113)
116 72.8 (58, 90.1)
37.2
113 (81.4, 153)
41.7
101 (72.6, 136)
All malignant neoplasms
42 0.4
..
0.5
..
Malignant neoplasms of the lip, oral cavity and pharynx
0
Malignant neoplasms of digestive organs and peritoneum
8
6.9
115 (49.8, 227)
7.6
105 (45.4, 207)
1
407 (111, 1040)
1.1
362 (98.6, 926)
Malignant neoplasms of the stomach
4
Malignant neoplasms of respiratory and intrathoracic organs
15 7.4
204 (114, 336)
9.9
151 (84.7, 250)
Malignant neoplasms of trachea, bronchus and lung
15 7.1
210 (118, 346)
9.6
157 (87.6, 258)
Malignant neoplasm of the pleura
0
0
..
0
..
Malignant neoplasms of other genitourinary organs
2
5.5 36.3 (4.4, 131)
6.3 31.7 (3.8, 115)
Malignant melanoma of the skin
1
0.6
..
0.5
..
Other malignant neoplasm of the skin
0
0
..
0
..
Malignant neoplasm of the breast
10 9.4
106 (50.9, 195)
9.6
104 (49.9, 192)
Malignant neoplasm of the uterus
0
0.5
..
0.6
..
Malignant neoplasm of the ovary
1
2.4 40.8 (1, 228)
2.6 38.7 (1, 216)
Malignant neoplasm of the thyroid gland
0
0.1
..
0.1
..
Malignant neoplasms of the lymphatic and haematopoietic tissue
2
2.4
85 (10.3, 307)
2.4 84.4 (10.2, 305)
Multiple myeloma
0
0.3
..
0.3
..
.. Leukaemia
1
0.8
..
0.9
1
Leukaemia, except chronic lymphatic leukaemia
0.8
..
0.8
..
Malignant neoplasm of the brain and central nervous system
0
1.4
..
1.4
..
Malignant neoplasm of the brain
0
1.3
..
1.3
..
Benign neoplasms
0
0.1
..
0.1
..
Neoplasms of uncertain or unspecified behaviour
0
0.2
..
0.3
..
All neoplasms
42 37.5
112 (80.6, 151)
42.1 99.7 (71.8, 135)
Diseases of the blood and blood forming organs
0
0.2
..
0.3
..
Diseases of the circulatory system
13 20.1 64.5 (34.4, 110)
26.9 48.4 (25.8, 82.8)
Diseases of the respiratory system
6
6.5 92.5 (33.9, 201)
9.1 66.3 (24.3, 144)
Diseases of the genitourinary system
1
0.9
..
1.2
..
.. SMRs not calculated where both the observed and expected deaths <2 14
Table 2.7 Male cancer registrations by disease group: numbers of cases and SRRs with and without adjustment for deprivation
Observed
Unadjusted for deprivation
Adjusted for deprivation Disease group
registrations Expected
SRR (95% CI)
Expected
SRR (95% CI) All malignant neoplasms
62
66.1
93.7 (71.9, 120)
68.7
90.2 (69.1, 116)
All malignant neoplasms, excluding non-melanoma skin 51
52.3
97.4 (72.6, 128)
55.2
92.3 (68.8, 121)
cancer 2
2.7
75.1 (9.1, 271)
3.2
63.5 (7.7, 229)
Malignant neoplasms of the lip, oral cavity and pharynx Malignant neoplasms of digestive organs and
15
11.7
128 (71.7, 211)
12.5
120 (67.3, 198)
peritoneum
Malignant neoplasms of the stomach
1
1.7
..
2
..
Malignant neoplasms of respiratory and intrathoracic
7
8.9
78.3 (31.5, 161)
10.5
66.5 (26.8, 137)
organs Malignant neoplasms of trachea, bronchus and lung
4
7.5
53 (14.4, 136)
8.9
45.1 (12.3, 116) Malignant neoplasm of the pleura
0
0
Malignant neoplasms of other genitourinary organs
11
13.4
82.2 (41.1, 147)
13.3
82.4 (41.1, 147) Malignant melanoma of the skin
3
3.2
92.4 (19.1, 270)
3
100 (20.7, 293) Other malignant neoplasm of the skin
11
13.8
79.7 (39.8, 143)
13.5
81.6 (40.7, 146) Malignant neoplasm of the thyroid gland
Malignant neoplasms of the lymphatic and
haematopoietic tissue Multiple myeloma
0
0.5
6
6.8
88.8 (32.6, 193)
6.8
87.6 (32.2, 191)
2
0.6
349 (42.2, 1260)
0.6
346 (41.8, 1250) Leukaemia
0
1.7
..
1.7
..
Leukaemia, except chronic lymphatic leukaemia Malignant neoplasm of the brain and central nervous system
Malignant neoplasm of the brain 0
1.2
..
1.2
..
4
2
4
1.9
0
In situ neoplasms
.. SRRs not calculated where both the observed and expected registrations <2
15
2.6
..
..
199 (54.3, 511)
206 (56, 526)
- (0, 144)
0
0.5
2
1.9
2.5
..
..
203 (55.2, 519)
209 (57, 535)
- (0, 148)
Table 2.8 Female cancer registrations by disease group: numbers of cases and SRRs with and without adjustment for deprivation
Observed
Unadjusted for deprivation
Adjusted for deprivation
Disease group
registrations Expected SRR (95% CI)
Expected SRR (95% CI)
All malignant neoplasms 122
118 103 (85.8, 123)
119 102 (84.9, 122)
All malignant neoplasms, excluding non-melanoma skin cancer 105
101 104 (84.9, 126)
104 101 (82.8, 123)
Malignant neoplasms of the lip, oral cavity and pharynx 3
1.6 183 (37.7, 534)
1.9 155 (32, 453)
Malignant neoplasms of digestive organs and peritoneum
15
11.9
126 (70.6, 208)
12.4
121 (67.7, 200)
Malignant neoplasms of the stomach
5
1.4
370 (120, 863)
1.6
312 (101, 729)
Malignant neoplasms of respiratory and intrathoracic organs
16
8.9
179 (102, 291)
12.1
132 (75.5, 215)
Malignant neoplasms of trachea, bronchus and lung
16
8.3
194 (111, 315)
11.1
144 (82.3, 234)
Malignant neoplasm of the pleura
0
0
Malignant neoplasms of other genitourinary organs
11
16.4
66.9 (33.4, 120)
18.1
60.6 (30.3, 108)
Malignant melanoma of the skin
5
6.1
82 (26.6, 191)
5
99.4 (32.3, 232)
Other malignant neoplasm of the skin
17
16.9
100 (58.5, 161)
15.7
109 (63.2, 174)
Malignant neoplasm of the female breast
46
39.5
116 (85.2, 155)
37.6
123 (89.7, 163)
Malignant neoplasm of the uterus
2
3.6
54.9 (6.6, 199)
3.6
55.3 (6.7, 200)
5.6
1.7
6.2
0.6
1.7
1.3
1.7
1.6
89.4
71.8 (19.6, 184)
..
64.2 (17.5, 164)
..
..
..
..
..
83.9 (66, 105)
5.5
1.5
6
0.5
1.6
1.2
1.6
1.6
92.4
72.8 (19.8, 187)
..
66.6 (18.1, 171)
..
..
..
..
..
81.2 (63.9, 102)
Malignant neoplasm of the ovary
4
Malignant neoplasm of the thyroid gland 0
Malignant neoplasms of the lymphatic and haematopoietic tissue 4
Multiple myeloma 0
Leukaemia
1
Leukaemia, except chronic lymphatic leukaemia 1
Malignant neoplasm of the brain and central nervous system
0
Malignant neoplasm of the brain 0
In situ neoplasms
75
.. SRRs not calculated where both the observed and expected registrations <2
16
..
0
..
Table 2.9 Male cancer registrations by disease group and time since first employment: numbers of cases and SRRs with adjustment for
deprivation
≥10 years since first employment
<10 years since first employment
Observed
Adjusted
Observed
Adjusted
Disease group
registrations
SRR (95% CI)
registrations
SRR (95% CI)
All malignant neoplasms
21
91.4 (56.6, 140)
41
89.6 (64.3, 122)
All malignant neoplasms, excluding non-melanoma skin cancer
19
99.5 (59.9, 155)
32
88.6 (60.6, 125)
Malignant neoplasms of the lip, oral cavity and pharynx
0
..
2
90.5 (11, 327)
Malignant neoplasms of digestive organs and peritoneum
1
27.9 (0.7, 155)
14
158 (86.2, 264)
Malignant neoplasms of the stomach
0
..
1
..
Malignant neoplasms of respiratory and intrathoracic organs
2
66.7 (8.1, 241)
5
66.5 (21.6, 155)
Malignant neoplasms of trachea, bronchus and lung
1
40 (1, 223)
3
47.1 (9.7, 138)
Malignant neoplasm of the pleura
0
..
0
..
Malignant neoplasms of other genitourinary organs
6
118 (43.5, 258)
5
60.4 (19.6, 141)
Malignant melanoma of the skin
1
..
2
115 (13.9, 414)
Other malignant neoplasm of the skin
2
51.6 (6.2, 186)
9
93.7 (42.9, 178)
Malignant neoplasm of the female breast
0
..
0
..
Malignant neoplasm of the uterus
0
..
0
..
Malignant neoplasm of the ovary
0
..
0
..
Malignant neoplasm of the thyroid gland
0
..
0
..
Malignant neoplasms of the lymphatic and haematopoietic tissue
3
102 (21, 298)
3
76.9 (15.9, 225)
Multiple myeloma
0
..
2
474 (57.4, 1710)
Leukaemia
0
..
0
..
Leukaemia, except chronic lymphatic leukaemia
0
..
0
..
Malignant neoplasm of the brain and central nervous system
3
338 (69.7, 987)
1
..
3
..
351 (72.4, 1030)
1
Malignant neoplasm of the brain
In situ neoplasms
0
..
0
..
.. SRRs not calculated where both the observed and expected registrations <2
17
Table 2.10 Female cancer registrations by disease group and time since first employment: numbers of cases and SRRs with adjustment
for deprivation
≥10 years since first employment <10 years since first employment
Observed
Adjusted
Observed
Adjusted
Disease group
(95% CI)
(95% CI) registrations
SRR
registrations
SRR
All malignant neoplasms 39
110 (78.4, 151)
83
98.8 (78.7, 123)
All malignant neoplasms, excluding non-melanoma skin cancer 37
117 (82.5, 162)
68
94.3 (73.2, 120)
Malignant neoplasms of the lip, oral cavity and pharynx 0
..
3
208 (42.9, 608)
Malignant neoplasms of digestive organs and peritoneum
5
170 (55, 396)
10
106 (50.7, 195)
Malignant neoplasms of the stomach 3
701 (145, 2050)
2
171 (20.6, 616)
Malignant neoplasms of respiratory and intrathoracic organs 7
277 (111, 570)
9
93.9 (42.9, 178)
Malignant neoplasms of trachea, bronchus and lung 7
309 (124, 637)
9
102 (46.5, 193)
Malignant neoplasm of the pleura 0
..
0
..
Malignant neoplasms of other genitourinary organs 5
69.7 (22.6, 163)
6
54.7 (20.1, 119)
Malignant melanoma of the skin 1
47.5 (1.2, 265)
4
137 (37.3, 351)
Other malignant neoplasm of the skin 2
52.3 (6.3, 189)
15
127 (70.9, 209)
17
156 (91, 250)
29
109 (72.8, 156)
Malignant neoplasm of the female breast
0
..
2
72 (8.7, 260)
Malignant neoplasm of the uterus 2
112 (13.6, 405)
2
54 (6.5, 195)
Malignant neoplasm of the ovary
0
..
0
..
Malignant neoplasm of the thyroid gland 1
46.7 (1.2, 260)
3
77.6 (16, 227)
Malignant neoplasms of the lymphatic and haematopoietic tissue 0
..
0
..
Multiple myeloma ..
1
..
Leukaemia
0
0
..
1
..
Leukaemia, except chronic lymphatic leukaemia 0
..
0
..
Malignant neoplasm of the brain and central nervous system
0
..
0
..
Malignant neoplasm of the brain 47
85.2 (62.6, 113)
28
75.2 (50, 109)
In situ neoplasms
.. SRRs not calculated where both the observed and expected registrations <2
18
Table 2.11 Female lung cancer registrations: numbers and SRRs by time since
first employment for selected subgroups
≥10 years since first
<10 years since first
Total
employment
employment Total
N
7
9
16
Unadjusted SRR
423 (170, 872) 136 (62.3, 259)
194 (111, 315)
Adjusted SRR
309 (124, 637) 102 (46.5, 193)
144 (82.3, 234)
Employed 12 months or more
N
4
Unadjusted SRR
417 (114, 1070) Adjusted SRR
301 (81.9, 770) Aged <50 years
N
Unadjusted SRR
Adjusted SRR
9
149 (68, 283)
111 (50.9, 211)
3
372 (76.7, 1090) 267 (55.1, 780) 1
..
..
13
186 (98.8, 317)
138 (73.5, 236)
4
190 (51.8, 487)
138 (37.5, 353)
Aged 50 years or more
N
4
Unadjusted SRR
472 (129, 1210) Adjusted SRR
350 (95.5, 897) 8
151 (65.1, 297)
113 (48.9, 223)
12
195 (101, 341)
146 (75.6, 256)
First employed before 1982
N
1
Unadjusted SRR
..
Adjusted SRR
..
7
171 (68.9, 353)
129 (51.9, 266)
8
170 (73.3, 335) 127 (55, 251) First employed 1982 or later
N
6
Unadjusted SRR
583 (214, 1270) Adjusted SRR
426 (156, 926) 2
79.3 (9.6, 286)
58.5 (7.1, 211)
8
225 (97.3, 444)
166 (71.5, 326)
Fab workers
N
Unadjusted SRR
Adjusted SRR
7
146 (58.6, 300)
109 (43.7, 224)
14
232 (127, 389)
172 (94.2, 289)
7
569 (229, 1170) 416 (167, 857) Non-fab workers
N
0
2
2
Unadjusted SRR
..
111 (13.4, 400)
89.7 (10.9, 324) Adjusted SRR
..
83.4 (10.1, 301)
67.1 (8.1, 243) .. SRRs not calculated where both the observed and expected registrations <2
Table 2.12 Female lung cancer registrations: numbers and SRRs by duration of
employment
Duration of employment
n
<1 year
1-4 years
5-9 years
10 or more years
3
3
5
5
SRR 95% CI
239
211
288
130
19
(49.3, 699)
(43.6, 617)
(93.6, 673)
(42.1, 303)
Table 2.13 Female stomach cancer registrations: numbers and SRRs by time
since first employment for selected subgroups
≥10 years since <10 years since first
Total employment
first employment
Total N
3 2
5
Unadjusted SRR
800 (165, 2340) 205 (24.8, 739)
370 (120, 863)
Adjusted SRR
701 (145, 2050) 171 (20.6, 616)
312 (101, 729)
Employed 12 months or more
N
3 Unadjusted SRR
1170 (241, 3420) Adjusted SRR
1030 (213, 3020) Aged <50 years
N
Unadjusted SRR
Adjusted SRR
2
224 (27.1, 809)
187 (22.6, 675)
3 1160 (239, 3380) 1030 (213, 3010) 1
..
..
5
435 (141, 1020)
367 (119, 857)
4
677 (185, 1730)
576 (157, 1480)
Aged 50 years or more
N
0 Unadjusted SRR
.. Adjusted SRR
.. 1
..
..
First employed before 1982
N
2 Unadjusted SRR
1520 (184, 5490) Adjusted SRR
1260 (153, 4560) 1
..
..
3
425 (87.6, 1240)
356 (73.4, 1040)
First employed 1982 or later
N
1
Unadjusted SRR
..
Adjusted SRR
..
1
..
..
2 310 (37.5, 1120) 264 (32, 955) Fab workers
N
Unadjusted SRR
Adjusted SRR
1
..
..
3
301 (62.1, 880)
254 (52.5, 744)
2 704 (85.2, 2540) 621 (75.2, 2240) 1
..
..
Non-fab workers
N
1
1
2 Unadjusted SRR
..
378 (9.4, 2100)
563 (68.1, 2030) Adjusted SRR
..
317 (7.9, 1770)
475 (57.4, 1710) .. SRRs not calculated where both the observed and expected registrations <2
Table 2.14 Female stomach cancer registrations: numbers and SRRs by duration
of employment
Duration of employment
n
SRR 95% CI
<1 year
0
..
1-4 years
0
..
5-9 years
4
1350 (367, 3450) 10 or more years
1
..
.. SRRs not calculated where both the observed and expected registrations <2
20
Table 2.15 Female breast cancer registrations: numbers and SRRs by time since
first employment for selected subgroups
<10 years since first ≥10 years since first
Total
employment
employment Total N
17
29
46
103 (69.2, 148)
116 (85.2, 155)
Unadjusted SRR
148 (86.4, 238) 109 (72.8, 156)
123 (89.7, 163)
Adjusted SRR
156 (91, 250) Employed 12 months or more
N
6
Unadjusted SRR
75.9 (27.8, 165) Adjusted SRR
80 (29.4, 174) 27
107 (70.6, 156)
113 (74.3, 164)
33
99.6 (68.6, 140)
105 (72.2, 147)
Aged <50 years
N
Unadjusted SRR
Adjusted SRR
10 113 (54.3, 208) 119 (57.2, 219) 10
74.5 (35.7, 137)
78.6 (37.7, 145)
20
89.9 (54.9, 139)
94.8 (57.9, 146)
Aged 50 years or more
N
7 Unadjusted SRR
267 (107, 550) Adjusted SRR
280 (113, 578) 19
130 (78.1, 203)
136 (81.9, 212)
26
151 (98.3, 221)
158 (103, 231)
First employed before 1982
N
1 Unadjusted SRR
33.8 (0.8, 188) Adjusted SRR
35.4 (0.9, 198) 10
78.4 (37.6, 144)
82.4 (39.5, 152)
11
70 (34.9, 125)
73.5 (36.7, 132)
First employed 1982 or later
N
16 Unadjusted SRR
188 (108, 306) Adjusted SRR
199 (114, 322) 19
124 (74.7, 194)
131 (78.6, 204)
35
147 (102, 204)
155 (108, 215)
Fab workers
N
Unadjusted SRR
Adjusted SRR
13 146 (77.5, 249) 153 (81.6, 262) 26
121 (78.9, 177)
127 (83, 186)
39
128 (91, 175)
135 (95.8, 184)
Non-fab workers
N
Unadjusted SRR
Adjusted SRR
4 158 (43.2, 406) 167 (45.4, 427) 3
45.9 (9.5, 134)
48.2 (10, 141)
7
77.3 (31.1, 159)
81.2 (32.6, 167)
Table 2.16 Female breast cancer registrations: numbers and SRRs by duration of
employment
Duration
n
SRR 95% CI
<1 year
13
203 (108, 347)
1-4 years
8
85.7 (37, 169)
5-9 years
6
77.5 (28.4, 169)
10 or more years
19
118 (71.3, 185)
21
Table 2.17 Male colorectal cancer registrations: numbers and SRRs by time since
first employment for selected subgroups
<10 years since
first employment
≥10 years since
first employment
Total
Total
N
Unadjusted SRR
1
..
10
235 (113, 433)
11
186 (93, 333)
Employed 12 months or More N
Unadjusted SRR
1
..
8
201 (86.9, 396)
9
179 (81.8, 339)
Aged <50 years
N
Unadjusted SRR
0
..
2
150 (18.2, 542)
2
94.1 (11.4, 340)
Aged 50 years or more
N
Unadjusted SRR
1
..
8
275 (119, 541)
9
238 (109, 452)
First employed before
1982
N
Unadjusted SRR
0
..
6
259 (94.9, 563)
6
218 (80.1, 475)
First employed 1982 or Later
N
Unadjusted SRR
1
..
4
208 (56.6, 532)
5
159 (51.4, 370)
Fab workers
N
Unadjusted SRR
0
..
4
305 (83.2, 782)
4
201 (54.8, 515)
Non-fab workers
N
1
6
7
Unadjusted SRR
..
204 (75, 445)
179 (71.9, 368)
.. SRRs not calculated where both the observed and expected registrations <2
Table 2.18 Male colorectal cancer registrations: numbers and SRRs by duration of
employment
Duration
<1 year
1-4 years
5-9 years
10 or more years
n
2
3
3
3
SRR
230
198
277
123
22
95% CI
(27.8, 830)
(40.9, 579)
(57.1, 808)
(25.4, 360)
3 HISTORICAL HYGIENE ASSESSMENT
3.1
INTRODUCTION
A Historical Hygiene Assessment (HHA) was undertaken with the aim of gathering
information about processes, working practices and working conditions at NSUK since the
plant opened in 1972. The intention of the assessment was to gather both documentary
evidence and information from interviews with past and present employees.
3.2
DOCUMENTARY RECORDS
IOM provided NSUK with details of the range of documentary information they wished to
access to assist with the HHA process. These were:











Site plans
Control of Substances Hazardous to Health (COSHH) assessments
Occupational hygiene measurement data
Details of ionising and non-ionising radiation sources present at NSUK
Details of continuous monitoring systems
Details of Personal Protective Equipment (PPE) / Respiratory Protective
Equipment (RPE) Smoking / health surveillance policies Accident / incident reports Shift pattern records Fabrication areas, production processes and job titles Details of key automation / process changes in the wafer fabrication area NSUK provided photocopies of a range of historical documents to assist with the HHA
process. These included site diagrams, process guidance notes, COSHH risk assessments,
accident and incident records, occupational hygiene reports by the National Radiation
Protection Board and a copy of a previous safety policy. The documents were reviewed and
followed up via personal communication with staff members for further information or
clarification as necessary. A summary report of the information contained in all these
records was drafted and circulated for comment to NSUK, who confirmed that they were
factually correct.
Documentary records held by the Health and Safety Executive (HSE) offices in Glasgow
were reviewed to identify any additional relevant information. Phase Two, a support group
for NSUK workers, was also given the opportunity to provide appropriate documentary
records which they felt could assist with the HHA process.
3.3
INTERVIEWS WITH LONG-SERVING EMPLOYEES
IOM supplied NSUK and Phase Two with details of the characteristics of those individuals
they wished to interview. These were:





employed long-term in the plant: at least five years, possibly 10 years or more, and
ideally some employed during the early period of the plant’s history;
familiar with the process and chemicals used in the area they were employed;
have a wide view of the work process as a whole and where their area fits;
willing and able to be interviewed as part of this study; and
likely to contribute to the study in a fair and impartial manner.
23
Both NSUK and Phase Two made recommendations for current and previously employed
workers likely to provide useful information under this remit. The potential candidates for
the HHA interviews were provided with a participant information leaflet, which included
further background information on the project (example of participant information leaflet is
provided in the Supplementary Appendices13) and how the information collected during the
HHA process would be used. The leaflet gave a guarantee that participations and all the
original information collected would be kept strictly confidential, and that no document
produced would identify any individual.
Twenty-one long-serving employees were selected to participate in the HHA interview
process. An IOM researcher contacted each individual put forward by Phase Two to
confirm their agreement to participate in the study and arrange a convenient date and time
for the interview to take place. The names of employees put forward by NSUK, as well as
their availability, were supplied to IOM through NSUK’s personnel department.
Interviews with the selected informants were undertaken during 2007 to obtain their
knowledge of the historical development of the plant and the patterns of work within it, the
chemicals and other agents used in the various jobs and processes as well as how jobs,
conditions and working practices changed over time. Signed consent forms were obtained
from each of the participants, and all interviewees gave permission for audio recording of
their interview. All HHA interviews were carried out by the same experienced IOM
research occupational hygienist. Interviews with current NSUK employees took place on
NSUK premises during their normal working shift whereas the HHA interviews with exemployees took place at a central hotel in Greenock.
The HHA interviews were a three stage process as follows:
1. Initial interview with participant, which lasted approximately 1.5 to 2 hours.
2. Transcription of the interview using the digital recording and notes made during the
interview.
3. A final follow-up interview with the participant to allow them the opportunity to
read and comment on the interview transcript and the researcher the opportunity to
ask any additional questions or seek clarification.
The results of these interviews were combined with the documentary evidence, allowing
summary descriptions to be made of the various processes and the chemicals and
substances involved. These descriptions are contained in the supplementary document14.
Within that document, the identities of the HHA interviewees are not disclosed, no details
are attributed to any interviewee, and care has been taken to maintain confidentiality on
sensitive issues.
24
4 CASE-CONTROL AND CASE-ONLY SURVEY – METHOD
AND RESULTS
4.1 ELIGIBILITY OF CASES FOR THE CASE-CONTROL AND CASE-ONLY
STUDIES
The case-control and case-only studies included all confirmed cases of the cancers of
interest among the cohort of NSUK workers and ex-workers that were notified to the study
team prior to the commencement of interview phase of the study.
4.1.1
Cases not in the original study cohort
A few potential cases who were not members of the original cohort identified themselves to
HSE following publicity about the initial study findings and plans for a follow-up study.
These cases were eligible for the case-control or case-only studies if we could obtain the
following:
(i) documentary evidence that they were employed by NSUK at Greenock (e.g. letter of
appointment, payslip, etc.); and
(ii) confirmation that they had been diagnosed as having one of the four cancers of interest
(from their GP and/or Hospital Consultant).
4.2 ELIGIBILITY FOR CONTROLS
For each case, potential controls were: 1) Women from within the cohort; 2) Whose date of birth was within five years either side of the case’s date of birth; 3) Who were alive at the time of the event defining the case; and 4) Whose date of first joining NSUK was earlier than the time of the event defining the
case; i.e. who were already in the study at that time. Controls who were known to have developed any type of cancer by the time of the defining
event were not included, although they were not excluded if they developed any cancer
subsequent to that date.
4.3 SAMPLING METHODOLOGY FOR CONTROLS
Potential controls for each case were selected using SPSS Version 159 using the eligibility
criteria in Section 4.2. From this list, four controls plus two reserves were selected per case
using probability sampling (without replacement) in STATA Version 810. For subsequent
rounds of control recruitment, a macro in Excel 2003 was developed and used instead,
which also included an audit of selection and de-selection. This enabled successive rounds
of control selection to take place, without the need to cross-reference and carry out checks
across the two software packages.
Controls were randomly selected irrespective of their current vital status. For practical
reasons and to aid simplicity, controls were matched to only one case.
Before the first round of control selection, it was agreed to select a further four controls per
case (using the Excel macro). This was in response to the fact that the positive response rate
of cases to participate in the study was approximately 50%, and it was surmised that the
positive response rate for controls would be lower than for cases. It was hoped that by
increasing the number of controls to 10 per case, the desired number of controls would be
attained, assuming a positive response rate of 40%.
25
4.4
THE RECRUITMENT PROCESS
Figure 4.1 (below) summarises the numbers of cases and controls recruited.
Figure 4.1 Summary of subjects recruited for the study
CASES
Case only
Live
Proxy
Total
Case control
Brain
Stomach
Lung
Breast
0/0
4/4 (100%)
4/4 (100%)
0/0
2/4 (50%)
2/4 (50%)
0/0
7/17 (41%)
7/17 (41%)
16/28 (57%)
7/12 (58%)
23/40 (58%)
TIME
CONTROLS*
Round 1
54/183 (30%)
Live
Proxy 3/11 (27%)
Total 57/194 (29%)
Round 2
27/112 (24%)
Live
0/6 (0%)
Proxy
Total 27/118 (23%)
Round 3
Live
Proxy
Total
7/32 (22%)
0/0
7/32 (22%)
88/327 (27%)
Live
Proxy 3/17 (18%)
Total 91/344 (26%)
TOTAL
Case-control summary
Total Breast cancer cases
Total controls
**21
***83
4 cases had 5 matched controls
15 cases had 4 matched controls
1 case had 3 matched controls
1 case had no matched controls
Notes:
* Control recruitment is explained in further detail in Section 4.4.4
** 2 recruited cases withdrew from the study prior to interview
*** 8 recruited controls withdrew from the study prior to interview
4.4.1
Alive cases and controls from original study cohort
Details of the live cases and controls were sent to the Practitioner Services Division (PSD)
in Glasgow who double-checked that the subject was still alive before sending any postal
26
correspondence. These subjects were approached by PSD via their GP, and included in the
initial approach to the GP was: a short letter; a form for the GP to complete and return to
HSE; two information leaflets on the study (one for the GP and one for the subject); the
results information leaflet from the initial study; an approach letter and a response form for
the study subject. These were sent out by PSD together in the same envelope, along with
two postage-paid envelopes (for replies from both the GP and subject). All of these
documents are available in the Supplementary Appendices13.
According to the Protocol3, HSE would notify PSD by telephone once a successful contact
was made with the subject. If PSD had not heard from HSE about a GP’s response in
relation to a subject within 10 working days, they would send one reminder letter to the
GP13, which would contain all the original enclosures together with a short covering
reminder letter. In practice, it was easier to notify PSD of the GPs who had not responded.
If a positive response was received from a GP, but a case subject did not respond within 10
to 20 working days, a similar method was used to send out reminders to the GP for passing
onto the patient. To limit the burden placed on GPs, PSD sent reminders directly to the
controls if their GP had agreed to forward the first invitation onto the patient.
4.4.2
Identification of proxy respondents for deceased cases and controls
For deceased cases and controls, proxy respondents were identified by approaching the
informant on death certificates. A definitive list of deceased cases and controls was sent to
the National Health Service Central Register (NHSCR) in Scotland who checked the vital
status of the informant from the death certificate (or informant of informant’s death if initial
informant was also deceased). They supplied HSE with confirmation that the informant was
alive, their health board/authority of residence, NHS number and address at time of the
decedent’s death. This information was forwarded by HSE to PSD Glasgow, who obtained
the informants’ current addresses so that they could be approached directly (in accordance
with Privacy Advisory Committee (PAC) clearances). The letter of approach was sent by
HSE, together with the information leaflet. Reminders were sent after around 4 weeks, and
a questionnaire was included to enable informants to respond by mail rather than telephone
if they preferred to do so. All of these documents are available in the Supplementary
Appendices13. Where informants felt they were unable to provide the necessary detail of
information about the deceased, then they were asked if there was another appropriate
person who could be approached. For non-NSUK work and personal/ lifestyle factors, we
sought information from a relative who could provide details on the full life history of the
subject. For work at NSUK, information was sought from a suitable co-worker (and/or the
same relative) who may also have been able to provide supplementary information about
lifestyle factors, e.g. smoking habits.
4.4.3
Cases occurring outside Scotland
It was not possible to replicate the above method for contacting a small number of
individuals resident in England rather than Scotland. However, PSD were able to identify
the English region in which these individuals were registered as patients, and Primary Care
Trusts were then asked to identify individuals’ GPs. Thereafter, the recruitment process was
identical to that for live Scottish subjects.
4.4.4
Progress of control recruitment
Three rounds or recruiting were required to ensure that as many cases as possible had four
matched controls, and the approach at each round was driven pragmatically in the light of
subjects recruited from the previous round (for example, in the first round, 10 potential
controls were contacted to recruit 4 controls, whereas for second and third rounds, five
27
potential controls were contacted per remaining control required in each round). Figure 4.1
(at the start of this section) summarises the recruitment process.
A situation arose where one control had already been interviewed before we knew the case
had withdrawn from the study. It was decided that this control could be matched to another
case who met the matching criteria, with an event date within a year.
During the second and third rounds, some of the cases had more than four controls. Rather
than dismissing these extra controls in the study, we decided to create an ‘excess control
pool’, so that controls could be allocated to a different case (but still meeting the matching
criteria). Controls matching to fewer cases were selected as controls first. This meant that
there was more versatility, as the pooled controls could be matched to various cases. When
controls could not be matched to a case that had fewer than four controls, the control was
matched to a case who already had four controls, and in some cases, five controls.
We judged that this approach would not have an important effect on the randomness of
selection, and as recruiting controls was becoming an increasingly difficult task (as the
numbers of potential controls for each case were falling) we decided it was better to
allocate the controls rather than omit them from the study altogether.
28
4.5
4.5.1
INTERVIEWS
Recruitment of interviewer
One interviewer carried out all of the survey interviews. Because of the occupational and
health-oriented content of the questionnaires, a qualified and experienced occupational
health nurse was recruited for the interviewing.
The nurse was introduced to the objectives of the study and to the questionnaires and
associated flashcards in a training session run by the IOM researchers. She was encouraged
to attempt to obtain as much detail as possible from every participant and to complete as
much of the questionnaires as possible.
After the first few interviews the interviewing nurse gave feedback on the process, which
was generally satisfactory, and no amendments were made to the questionnaire or to the
interviewing process.
4.5.2
Arrangements for interviews
Each participant was contacted by telephone and at this time it was confirmed that they
were still willing to participate. A suitable interview date and time was then arranged and a
letter sent out to confirm the arrangements and place of interview.
Interviews were conducted either at a convenient local venue away from the workplace, at
the IOM offices or in the subjects home depending on their preference. One interview was
carried out by the same interviewer over the phone due to the subject living in England.
A number of people cancelled or failed to attend; in these instances they were contacted
again and if still willing to participate further arrangements were made to interview them.
During the interviews each subject was asked to complete 2 questionnaires, work history
and lifestyle. At the end, each interviewee was thanked, paid £20 for inconvenience and
offered travel expenses.
4.5.3
Proxy respondents
A number of the deceased subjects were represented by two proxies, one to complete the
work history and one to complete the lifestyle. In these cases it was typical for the work
history proxy to be a colleague and the lifestyle proxy to be a family member or friend. Due
to the nature of the questions in the work history questionnaire (which related to other jobs
as well as NSUK work) the lifestyle proxy was asked the work history questionnaire as
well, as it was felt that they may be more likely to answer questions on work history outside
of NSUK.
4.5.4
Preparation of questionnaires
For each interview arranged, a set of questionnaires was personalised using a mail-merge
with the identifying details (name, sex, date of birth, study identity number) of the subject,
and of the proxy respondent where appropriate. Specific time periods mentioned in the
questionnaire were tailored to be relevant to the qualifying date of the subject’s casecontrol set.
29
Prepared questionnaires were sent in batches by courier to the interviewing nurse and
returned to the IOM in the same way once complete. Fictional examples of the subject and
proxy questionnaires can be found in the Supplementary Appendices13.
4.5.5
Interview results
During phone calls to organise the interviews a small number of people withdrew or could
not be contacted. The numbers of interviews carried out are outlined in Table 4.1 below.
Table 4.1 A breakdown of all of those interviewed, both proxies and subjects,
those who withdrew and extra people recruited
Subjects
OneTwoTwo-proxy
Total
proxy
proxy
but one
subjects
subjects Subjects
withdrew
*
Number of interviews
carried out
94
15
10
2
116*
Number of subjects for
which info was provided
95
15
5
2
117
Number who did not
participate
3
2
2
7
one subject supplied information before the interview process
Of the 3 subjects who did not participate, one was not contactable, and 2 chose to withdraw
at time of phone contact. For two of the subjects requiring proxy respondents, it was not
possible to complete both proxies; in one case a proxy was not contactable, and in the other
case the proxy withdrew from the study. There were a further 5 recruited subjects who did
not participate as they had failed to respond to a written request to provide telephone details
to enable the study team to arrange interviews.
At the end of the interview process five subjects had two proxies representing them. Two of
these were recruited by the original proxy as they recommended using someone who knew
more about the subject’s working life.
Finally, two subjects ended up being represented by one proxy as the second proxy
withdrew from the study. In that case the remaining proxy was asked both questionnaires.
4.5.6
Additional false proxy respondents
As a number of subjects were represented by proxies it was of interest to examine how
reliable the proxy information was likely to be. To do this it was decided to ask live
subjects to recruit someone who would have acted as their proxy if they were not available;
these people were called false proxies. The aim was to compare the answers given by the
subject to the information provided about them by the false proxy and to evaluate how
accurate the false proxies were in describing the subjects work history.
Explanation of this validation study was given at the end of each subject’s interview and
the subject was asked whether they would be willing to help further by recruiting a false
proxy. If subjects were interested they were given an information pack to take away and
read, which included a leaflet outlining the aims of this additional part of the study and
consent forms, plus a similar information pack to give to the person they recruited as their
false proxy13.
30
If after reading this leaflet a person was still happy to take part in this validation of the
study they signed their consent form and sent it back to HSE and passed the second
information pack onto their prospective false proxy. The false proxy then sent their consent
form back if they were also happy to take part in the additional study.
As this phase of the study did not start until part-way through the interview process due to
delay in acquiring ethical approval, a number of people who had previously been
interviewed were contacted to determine whether they would like to take part in this
additional study. If they indicated that they would, they were then sent out the false proxy
study information pack and the same process was followed.
At this point the details of anyone who had agreed to take part in this extra study and the
contact details of their nominated false proxy was passed to the IOM and the same process
was used to arrange suitable interviews.
In some cases IOM researchers had to clarify the purpose of the extra study. If during this
phone call the subject decided not to take any further part, usually as they felt that they
could not find anyone suitable, they were removed from the list of possible participants.
4.6
4.6.1
DATA PROCESSING
Initial checks
Questionnaires which needed further clarification regarding the coding of occupational
details (see the following section) were given to the occupational hygienist who had carried
out the HHA and clarifications obtained, as below.
4.6.2
Data Clarifications
As multiple answers had been allowed for in the NSUK work history section of the
questionnaire and as it had been a long time since some of the subjects had worked at
NSUK, several of the completed questionnaires needed minor clarifications. Clarification
of these questionnaires was obtained through the occupational hygienist at the IOM, who
assessed all questionnaires which were difficult to interpret. The interviewer was consulted
where appropriate. Neither the interviewer nor the hygienist was aware of the case-control
status of the respondents. However, in a few instances, the subject disclosed their status to
the interviewer; in these cases the interviewer disregarded this information and did not pass
the fact on to any other member of the team. Below is a list of the types of missing,
incomplete or inconsistent information given by the respondents and details of how these
were dealt with. Most of this missing information was due to the respondents being unable
to recall the information.
 More than one job title per NSUK work history line (and time period)
o Used processes and tasks listed to determine the correct job title from the ones
given.
o Or divided the time period over the different job titles given and used the
building, department and processes stated on the work history line for each of
these time periods
 Multiple shift patterns were recorded on one work history line
o The dates of working each shift pattern were assigned based on the duration of
time worked in each shift, if this information was provided.
o Or the dates of working each shift pattern were assigned an equal percentage of
the time period of the work history line.
31
 The proportion of time spent on each task/process in a work history line was not given
o Each process/task listed in a given work history line was assigned an equal
percentage of the time worked in that work history line.
 Months were missing in the end or start dates
o July was used
 The end date of one job was different from the start date of the subsequent job in the
job history
o The end date month was used if the difference was 1 month
o Or if the difference was larger the time period between the two jobs was
entered as missing information.
 NSUK work in the job history and the NSUK work history had different start/end dates
o The most appropriate dates, after examination of the questionnaires, were used.
o Or if this was not possible the dates were left as the respondent reported.
 People entered free text rather than pre-assigned codes
o The hygienist assigned codes based on the information provided or created new
codes.
In one case, useable information on the work history of the subject was provided by both
the work-history proxy and the lifestyle proxy. We used the information from the work
history-proxy for NSUK work, since they provided more detail about NSUK processes;
whereas we used information from the lifestyle proxy for non-NSUK work, since they
provided more detail about this.
4.6.3
Data entry
A workbook was prepared in Microsoft Excel, with 14 worksheets, one corresponding to
each section of the questionnaires.
All the data from the questionnaires were input into the prepared spreadsheets. Following
this, the data were entered a second time, independently and blind to the first entry, into a
duplicate Excel workbook.
4.6.4
Data validation and finalisation
To detect differences between the two Excel files, the files were compared line by line
using the file-compare facilities of GenStat version 1215. Tallies of all variables were
produced to check for the use of correct codes. Discrepancies were resolved by consulting
the questionnaire and the occupational hygienist. In a few instances, subjects
inappropriately answered a question which was based on the preceding stem question and
which did not need to be answered. The answers to these questions were removed,
providing that the change did not alter the overall status of the subject. All corrections and
changes agreed were incorporated into a final version of the Excel workbook.
4.6.5
Derived variables
Subjects who reported drinking less than one alcoholic beverage per month were entered
into the spreadsheet as non-drinkers. Where ranges had been recorded for the number of
cigarettes smoked and alcoholic drinks consumed, the mean of the range was used.
32
For each alcoholic drink the associated number of units was obtained from the
classifications used by the NHS16. The percentage of alcohol in common Scottish brands of
alcoholic drinks was used to determine the appropriate units. Numbers of different drinks
consumed per week were converted to alcohol units using the table below.
Table 4.2 The alcoholic units in each type of alcoholic drink listed in the
questionnaire (according to the NHS)
Alcoholic Drink
Number of Units
Bottle (330 ml) of 5% Beer, Lager & Cider
1.7 Pint (568 ml) of 4.5% Beer, Lager & Cider
2.5 Bottle (275 ml) of 5% Alcopops
1.4 Medium measure (25 ml to 35 ml) of 38-40% Spirits
1.2 Large glass (250 ml) of 12% Wine & Champagne
3.0 To provide an estimate of smoking exposure, pack years were calculated for all current
smokers using the following formula.
Pack years =
Number of cigarettes smoked per day x Number of years smoked
20
Pack-years could not be calculated for ex-smokers as they did not report the number of
cigarettes they smoked per day.
4.7
EXPOSURE ASSESSMENT
The results from the HHA process were used to inform an exposure assessment of the work
histories collected by the questionnaires. For the detailed histories of work at NSUK, the
hazards chosen for assessment were:






Distinction between fab and non-fab work
Inhalation exposure to IARC Category 1 (carcinogenic to humans) and 2 (possibly
carcinogenic to humans) substances:
o antimony trioxide
o arsenic and arsenical compounds, including arsine
o carbon tetrachloride
o ceramic fibre (“Kaowool”)
o chromium trioxide and chromic acid
o sulphuric acid mist
o trichloroethylene
Inhalation exposure to groups of substances: o solvents
o acids
o toxic gases Exposures to radiation sources: o ionising radiation (IR)
o non-ionising radio frequency (RF) radiation
o non-ionising ultra-violet (UV) radiation
Shiftwork
Other factors such as accidents and incidents involving hazardous substances.
Throughout the history of NSUK, a variety of Personal Protective Equipment (PPE) has
been extensively used by those working in fabrication areas including gloves, gauntlets and
full sleeved garments, with various implements also being used to manipulate the wafers
and process to minimise contact with the wafers and consequently, the hazardous agents
33
used. It was therefore judged that dermal exposure did not contribute importantly to overall
exposure. Given the extensive use of face masks to protect the wafers from contamination,
exposure by ingestion was also deemed negligible. Non-inhalation exposures via dermal
and ingestion routes were not considered further.
It was originally intended that an exposure assessment would be made on whether a subject
had been a member of the emergency response team (ERT) during their employment at
NSUK. Only three respondents indicated that they had been a member of the ERT, with
only one providing any additional information. Therefore, no exposure assessment was
carried out for these responses.
For work in occupations outside NSUK, assessment was undertaken for exposure to:




Key hazardous substances and physical agents
o arsenic
o asbestos
o aliphatic and alicyclic hydrocarbon solvents
o aromatic hydrocarbon solvents o organic solvents o ionising radiation
o non-ionising radio-frequency (RF) radiation
o non-ionising ultra-violet (UV) radiation work at other semi-conductor manufacturing facilities shiftwork para-occupational exposure to asbestos. It was originally intended that exposure assessment would also be undertaken for exposure
to asbestos in non-NSUK job. However, no subject reported having worked with asbestos,
and so this assessment was abandoned.
Upon reviewing the information on employments at semiconductor manufacturing sites
other than NSUK, the information was insufficiently detailed to confirm with any degree of
reliability whether the subject worked in a fab area or to inform any assessment on specific
exposures. Subjects were also asked to provide details of accidents / incidents which they
were personally involved with at other semiconductor manufacturing sites. Upon review of
the individual responses to this question, it was apparent that none of the reported
accidents/ incidents occurred at a semiconductor manufacturing site, and therefore again no
assessment was made.
4.8
DEVELOPMENT OF EXPOSURE MATRICES
The aim of the exposure assessment was to create exposure matrices that would link
assessments of exposure to elements of the subjects’ work histories. An occupational
exposure matrix (EM) is a table classified by some occupational factor(s) (e.g. location,
occupation, job, task, or other relevant factors.), and sometimes (although not here) by
calendar time periods, and in which the elements of the table summarise or codify aspects
of exposure. EMs based on job titles are usually called Job-Exposure Matrices (JEMs) and
those based on tasks Task Exposure Matrices (TEMs). The contents of an EM may be
binary (exposed/not), or indicate probability of exposure, or categories of intensity, or
summaries of actual measurements, such as mean concentrations. In the present study,
occupational hygiene measurements were not available for the whole lifespan of NSUK; for
all areas of the semiconductor manufacturing process or in instances sufficiently detailed,
and it was judged that subjective estimates of intensities would not be sufficiently reliable,
so all the assessments were made on a binary basis.
34
The same occupational hygienist who performed the HHA constructed all of the exposure
matrices, except for that relating to the non-NSUK jobs, which used FINJEM, the Finnish
Job Exposure Matrix17.
Lists were created of the flashcard codes of NSUK work history that were reported during
interviews., these were augmented by the additional codes created for interviewee
responses not covered by the pre-prepared lists. For each code, and for each hazard
considered, the hygienist recorded a judgment as to whether the location or activity coded
had the potential to incur exposure to the hazard. Coding was 1 = yes; 2 = no, with
‘unknown’ coded as 3.
4.8.1
NSUK work
4.8.1.1 Fab area work
Both building/area and job codes (Section C of the work history questionnaire13) allowed a
distinction between fab and non-fab areas. Each building/area code was assessed with
respect to whether or not fab work was carried out in that area. Separately, each job title
code was also assessed for whether the job involved fab work.
4.8.1.2 Inhalation exposure assessment
It was judged that the best information on likely exposures was contained in the codes for
process (Section C of the work history questionnaire13). Each process code was assessed
and coded 1 = yes; 2 = no, with respect to whether there was potential exposure to each of
the following:
Category 1 and 2 carcinogens:






Antimony trioxide
Arsenic and arsenical compounds, including arsine
Carbon tetrachloride
Ceramic fibre (“Kaowool”)
Chromium trioxide and chromic acid
Sulphuric acid mist (we have assumed this as being processes where hot sulphuric
acid is used)
 Trichloroethylene
Groups of key substances:
 Solvents – this included n-butyl acetate; acetone; trichloroethane (aka Genklene);
methanol; isopropyl alcohol; xylene; waycoat resists
 Acids – this included fuming nitric; acetic; aluminium etch (phosphoric, acetic, and
nitric); EKC 922 organic photo-resist stripper; hydrochloric; hydrofluoric;
phosphoric; sulphuric; nitric; oxide etch (hydrofluoric acid, ammonium fluoride);
vapox etch (acetic acid; ammonium fluoride); phosphorous oxychloride; aqua regia
(nitric / hydrochloric acids); chromic acid.
 Toxic gases – this included arsine, phosphine, boron trichloride, silane,
dichlorosilane, hydrogen chloride, silicon tetrachloride.
4.8.1.3 Radiation sources
It was again judged that the best information on likely exposures was contained in the
codes for process (Section C of the work history questionnaire13). Each process code was
35
assessed and coded 1 = yes; 2 = no, with respect to whether there was potential exposure to
each of the following:



Ionising radiation
Non-ionising radio –frequency (RF) radiation
Non-ionising ultra-violet (UV) radiation
4.8.1.4 Shift work
IARC recently concluded that there is limited evidence in humans (and sufficient evidence
in animals) that shift work that involves circadian disruption is probably carcinogenic to
humans18. With respect to breast cancer there is evidence to suggest that shift work,
including night work, which involves any work during the period 11pm and 6am is possibly
a hazard. There is also some suggestion that higher light exposures on back or swing shifts
may also contribute to melatonin disruption or other biological effects that may increase
risk of developing cancer. Since the IARC monograph has not yet been published, advice
was sought from two IOM ergonomists to identify those shift patterns (which respondents
selected from) which would be likely to disrupt the circadian rhythms. For the purposes of
this assessment, night shift work was defined as any work that involved a period of 3 hours
or more between the hours of 11.00 pm and 6.00 am.19
For the shift patterns reported in Section C of the work history questionnaire13, an EM was
developed identifying those shift patterns that involved:



night work
rotational work
work that disrupted the circadian rhythm
This EM is shown in Appendix 4, Table A4.1. The shifts which may disrupt circadian
rhythm can include both night shift and rotational shift work. The EM in Table A4.1 shows
which shift patterns were considered to disrupt circadian rhythm.
4.8.1.5 Accidents/incidents involving hazardous substances at work
Some responses from the work histories were not assessed via EMs, but exposure
summaries were assigned directly from the questionnaire responses. Responses to Section
C of the work history questionnaire were individually assessed to identify:


4.8.2
whether the respondent had been involved in an accident / incident involving gases
or liquids,
whether it involved:
o acid spills or splashes
o a gas leak
o a radiation leak.
Non- NSUK work
4.8.2.1 Hazardous substances
The Finnish Job-Exposure Matrix (FINJEM) developed by the Finnish Institute of
Occupational Health17 provides occupation specific estimates on probability and level of
exposure to selected risk factors during key calendar periods. This tool was used to assess
the non-NSUK jobs’ exposures to the following hazards:
36


Radiation sources:
o Ionising radiation
o non-ionising radio-frequency (RF) radiation
o non-ionising ultra-violet (UV) radiation Hazardous substances: o Arsenic
o asbestos
o aliphatic and alicyclic hydrocarbon solvents
o aromatic hydrocarbon solvents o organic solvents. 4.8.2.2 Shift work
For the responses on shift patterns of non-NSUK jobs (Section B of the work history
questionnaire13), an exposure matrix was developed identifying those shift patterns which
involved



night work
rotational work
work that disrupted the circadian rhythm.
This EM is shown in Table A4.2, again the shifts which are considered to disrupt the
circadian rhythm are shown in this table.
4.8.2.3 Paraoccupational exposure to asbestos
In instances where subjects indicated that they had lived (and for what time period) with
family members who worked in high risk asbestos industries / jobs, these were individually
assessed to identify whether the subject had lived with them prior to 1970, the point at
which the Asbestos Regulations SI 1969/690 were introduced and after which many
occupational and para-occupational exposure to asbestos are likely to have been
substantially reduced.
4.9
4.9.1
EXPOSURE ASSIGNMENT
Assignment from exposure matrix
The data on individual subjects’ work histories, both at NSUK and elsewhere, comprised
lines with occupational information and start and finish dates. In order to construct
individual exposure estimates, these were combined with the information on the exposures
implied by those occupations, i.e. the EMs described in Section 4.8. Durations implied by
each line were calculated and tabulated against the hazards implied by the locations,
processes and job titles, to give a total duration of exposure to each hazard. From these, a
dichotomised variable was created to indicate ever / never exposed to that hazard, where
‘ever’ was categorised by a non-zero duration.
Durations and corresponding ever/never classifications were calculated truncating the work
histories, where necessary, at the qualifying date for the case-control set. Additional
calculations used earlier truncation dates, to allow for latency periods of 5 and 10 years.
37
All these calculations were carried out using the calculation and tabulation facilities of the
statistical software package GenStat Version 1215.
4.9.2
Exposures from NSUK work
Exposure metrics created from the exposure matrices comprised:
4.9.2.1 Fab / non fab work:


Ever / never worked in a fab area Total duration (years) worked in fab area(s) 4.9.2.2 Radiation sources:
Ever / never and duration (years) worked on a process with potential exposure to



Ionising Radiation Non-ionising radio-frequency (RF) radiation Non-ionising ultra-violet (UV) radiation 4.9.2.3 NSUK shift-work:
Ever / never and duration (years) worked on:



night work
rotational shift(s) shift work that disrupts the circadian rhythm
4.9.2.4 Exposure to key inhaled substances:
Ever / never and duration (years) worked on a process with potential exposure to










4.9.3
antimony trioxide arsenic and arsenical compounds, including arsine carbon tetrachloride trichloroethylene chromium trioxide, chromic acid ceramic fibre / kaowool sulphuric acid mist (processes using hot sulphuric acid) solvents acids toxic gases Exposures from non-NSUK work
The following exposure metrics were used relating to non-NSUK work.
4.9.3.1 Non-NSUK work
Each work history line involving a job outside NSUK was assigned a code from the ISCO
(68) scheme20, and these were converted to the job codes used within the FINJEM job
exposure matrix. The corresponding values for probability and intensity of exposure were
extracted for the following agents:
38







asbestos aliphatic and alicyclic hydrocarbon solvents aromatic hydrocarbon solvents organic solvents. Ionising radiation non-ionising radio-frequency (RF) radiation non-ionising ultra-violet (UV) radiation These were combined with the job dates and a cumulative exposure to each agent was
calculated.
4.9.3.2 Non-NSUK shift-work:
Ever / never and duration (years) worked on a process with potential exposure to



4.9.4
night work
rotational shift(s) shift work that disrupts the circadian rhythm
Assignment directly from questionnaire response
In several instances, classifications to ‘ever / never’ exposed categories for each individual
were carried out directly, based on the free-text questionnaire responses. Sections 4.9.4.1 4.9.4.3 describe the metrics assessed in this way.
4.9.4.1 Work at other semiconductor manufacturing sites:


Ever / never worked in other semiconductor manufacturing sites. Total duration worked in other semiconductor manufacturing sites. 4.9.4.2 Accidents/incidents involving hazardous substances at NSUK:
Ever / never involved in an accident / incident involving:
 gases or liquids
 acid spills or splashes
 a gas
 a radiation leak
4.9.4.3 Para-occupational exposure to asbestos:
Ever / never and total duration (years) lived with a family member employed in a high risk
industry / occupation:


at any time before 1970 (before the introduction of the Asbestos Regulations 1969).
39
4.10 STATISTICAL ANALYSIS
4.10.1 Descriptive analyses
For the cases of the four types of cancer, and for the controls of the breast cancer cases, the
extensive data collected from the questionnaires were summarised in a series of tables.
Variables recorded as binary or classified responses were tabulated as cell counts, while
continuous variables were summarised as means, medians and standard deviations. In some
cases the geometric mean and geometric standard deviation was presented.
Analyses comparing cases and matched controls, as here for breast cancer, depended on
comparisons within each case-control set, and it was not easy to design tables that show
these clearly, particularly for continuous variables. Instead, we displayed the comparisons
using a graph specifically designed for this purpose21 (See Section 4.11.2).
4.10.2 Formal statistical analyses
Since lung, brain and stomach cancer were case-only series, no formal statistical analyses
were carried out on these. Analysis of the comparisons between the breast cancer cases and
their controls used conditional logistic regression modelling, a modelling framework
designed specifically for matched case-control studies22. These analyses were carried out
using routines provided within the open-access statistical package R23.
Models were fitted to predictor variables classified as ever/never exposed, and where
possible also to continuously-scaled predictors, e.g. for durations of exposure. Models
were fitted to versions of these variables representing the status of subjects at the qualifying
date defining casehood within the case-control set, and to alternative variates calculated at
dates 5 and 10 years prior, to allow for latency effects.
Conditional logistic regression models including the various occupational exposures were
fitted with and without adjustment for smoking habits and alcohol consumption, and for
continuous exposure variables both on the original and logarithmic scales. The distribution
of the duration of exposure was skewed, with many subjects having little or no exposure
while some have high durations of exposure. Taking the log of the duration exposed should
have made the fitted line more resistant to extreme values. Before taking the logs of the
duration exposed, we replaced the zeros with a small number relative to the rest of the
durations (0.05 years) so they were still included in the analysis.
Because work history information obtained from proxies was clearly less detailed than that
obtained directly from subjects, the analyses were repeated, excluding proxy respondents.
Where the proxy represented a case, this implied that there would be no contribution from
that case-control set.
For all analyses, the influence of each included subject on the exposure-response regression
coefficient was quantified using the ‘influence residual’ of Pregibon24; this was defined as
(an estimate of) the change in the regression coefficient when that subject was omitted from
the analysis set. These subject-specific influence residuals were graphed, and the data for
the highest-influence subjects inspected by eye.
40
4.10.3 Presentation of results
Results from the case-control framework are given as odds ratios (with 95% confidence
intervals based on Poisson assumptions) for comparing the risk of casehood against its
absence; for continuous predictor variables they were in the form of regression coefficients
expressing change in risk per unit change in the predictor, while for binary or categorical
predictors they were relative risks in comparison with a reference group.
4.10.4 Graphical aids to interpretation
Matching in case–control studies complicates the graphical presentation of data. Studies are
often presented without graphical displays, or graphed with heavily grouped exposure
categories, which can make it hard to compare across studies. However, within each
matched set, it is the difference between the exposures of the case and the matched set of
controls that is important, and one option may be to plot the distribution of those
differences, possibly on a logarithmic scale (i.e. as ratios), perhaps as a histogram,
probability plot or box-and-whisker summary. We extended this idea, using graphs
designed to summarise case-control comparisons in another study21.
The data are shown in Figures 4.2 to 4.9 and in Appendix 1 Figures A1.1 to A1.8. In each
graph, the data points represent individual case-control sets. The x-axis is the geometric
mean exposure of the whole case–control set, log-scaled, and these are summarised by a
box-and-whisker plot above the graph frame. (The box stretches from the 25th to the 75th
percentile with a central line for the median; the whiskers extend to the 10th and 90th
percentile; and the highest 10% and lowest 10% of values are plotted individually. Box
widths were scaled to the square roots of the numbers of case–control sets.) The y-axis
shows the ratio of the case exposure duration to the geometric mean duration of its matched
controls, again these are summarised using a box-and-whisker plot, to the right of the graph
frame. Diagonal dotted lines indicate regions of constant exposure of cases.
In these graphs, different symbols have used to indicate points that were identified as most
influential in the conditional regression analyses, defined here by a change in the regression
coefficient (a deletion residual) greater than 20% of its standard error. Where this
corresponded to the deletion of a control as well as its case, the case-control set is indicated
with a downward pointing triangle (▼); for the deletion of an influential case (and
therefore all its matched controls), a solid upward pointing triangle (▲) is used.
4.11 RESULTS
4.11.1 Description of lifestyle information
The questionnaires for all brain, lung and stomach cancer cases were completed by proxies.
Approximately 33% of breast cancer case questionnaires were completed by a proxy as
opposed to only 2% of breast cancer controls (Table 4.3)
Table 4.3. Number of cancer cases and controls by subject or proxy status
Case and Control Status Subject and
Breast
Breast
Stomach
Proxy Status
Brain Case Lung Case
Case
Control
Case
Subject
14
81
0
0
0
Proxy
7
2
4
7
2
Total
21
83
4
7
2
41
Total
95
22
117
All of the following descriptive tables include all subjects and proxies.
4.11.1.1 Gender
All four of the brain cancer cases were males and all of the lung cancer, stomach cancer and
breast cancer cases and controls were female.
4.11.1.2 Birth Year
Overall, those in the earlier birth decades attained a lower level of education compared to
those in the later birth decades.
Table 4.4 Cancer cases and controls by birth decades
Cases and
Birth decades Controls
1930-1939 1940-1949 1950-1959
Breast Case
5
8
5
Breast Control
15
32
21
Brain Case
0
2
0
Lung Case
3
4
0
Stomach Case
0
1
1
Total
23
47
27
1960-1969
3
15
2
0
0
20
Total
21
83
4
7
2
117
Table 4.5 Education level attained by birth decades for all subjects
Birth decades
Education level
19301940- 1950- 19601939
1949 1959 1965
Higher and Further Education Qualifications
1
5
8
13
School Education Qualifications
1
6
6
3
No Qualifications
21
36
13
4
Total
23
47
27
20
Total
27
16
74
117
4.11.1.3 House Type
The majority of subjects lived in a house or bungalow rather than a flat, maisonette or
apartment. No subjects lived in a mobile or temporary structure.
Two-thirds owned their property outright or with a mortgage/loan and one third lived in
rented accommodation. None of the subjects lived in rent free accommodation (Table 4.6).
Table 4.6 Type of house lived in by whether the house was owned or rented
Owned or Rented
House Type
Owned outright, or with
Rented
Total
mortgage/loan
Whole house or bungalow
59
22
81
Flat, maisonette or apartment
20
16
36
Total
79
38
117
4.11.1.4 Residences
The subjects provided details of each address they had lived at throughout their lifetime to
date. A total of 731 addresses were reported for all 117 subjects. Table 4.7 shows the
geographical distribution of the reported addresses.
42
Table 4.7 Total number of reported addresses by region for all subjects
Region
Total
Inverclyde*
580
Scotland other than Inverclyde
95
26
Outside UK
England
25
2
Northern Ireland
Wales
1
2
Don't Know
Total
731
* Inverclyde includes: Greenock, Gourock, Port Glasgow, Inverkip, Wemyss Bay,
Kilmacolm and Skelmerlie
The vast majority of addresses reported were in Inverclyde with 56% of the 117 subjects
having lived only in Inverclyde throughout their lives and another 19% having lived only in
Inverclyde and elsewhere in Scotland throughout their lives.
4.11.1.5 Fruit and vegetables
The majority of subjects ate less fresh fruit and vegetables as a child than they currently do
(Table 4.8). The same pattern was seen for each cancer type and both the breast cancer
cases and controls.
Table 4.8 Amount of fresh fruit and vegetables eaten at present and compared to
as a child for all subjects.
Number of
Amount of fresh fruit and vegetable eaten as a child compared to at
fresh fruit
present
and
vegetables
Much
A bit
About
A bit
Much
Don't
eaten at
Total
more
more
the same
less
less
know
present
6 or more a
0
0
0
0
1
0
1
day
4 or 5 a day
1
0
1
7
5
0
14
2 or 3 a day
2
10
12
10
14
0
48
One a day
1
4
10
3
11
1
30
5 or 6 a week
0
0
0
0
2
0
2
2 to 4 a week
0
0
2
1
2
0
5
One a week
0
1
2
0
3
0
6
1 to 3 per
month
Less often or
never
Don't know
1
0
5
0
1
1
8
0
0
2
0
0
0
2
0
0
1
0
0
0
1
Total
5
15
35
21
39
2
117
The majority of subjects ate about the same amount or less cooked green vegetables as a
child compared to now (Table 4.9). The same pattern was observed for each of the cancer
types and both the breast cancer cases and controls. One respondent did not answer this
question.
43
Table 4.9 Amount of cooked green vegetables eaten at present and compared to
as a child for all subjects.
Number of
Amount of cooked green vegetables eaten as a child compared to at
cooked green
present
vegetables
eaten at
Much
A bit
About
A bit Much
Don't
Total
present
more
more
the same
less
less
know
6 or more a
0
0
0
1
0
0
1
day
4 or 5 a day
1
0
3
4
3
0
11
2 or 3 a day
5
13
22
6
23
0
69
One a day
1
4
12
5
1
1
24
5 to 6 a week
0
0
1
0
0
0
1
2 to 4 a week
0
0
3
0
0
0
3
One a week
0
0
1
3
0
0
4
1 to 3 per
0
0
3
0
0
0
3
month
Total
7
17
45
19
27
1
116
4.11.1.6 Drinking
Of the 29 respondents who stated they were not current drinkers, 24 had always been non­
drinkers, 1 was an ex-drinker (a breast cancer control) and the remaining 4 did not respond
to the question. As the four who did not respond to the question had stated that they were
not current drinkers, the four were classified as non-drinkers. The one respondent who was
an ex-drinker stopped drinking at the age of 21. (Tables 4.10 and 4.11)
Table 4.10 Drinking status by cancer case and control
Breast
Breast
Brain
Lung Stomach
Drinking Status
Case
Control
Case
Case
Case
Current Drinker
18
61
3
4
1
Non-Drinker
3
22
1
3
1
Total
21
83
4
7
2
Total
88
29
117
Table 4.11 Average number of alcoholic drinks per week and average number of
units of alcohol per week for breast cancer cases, breast cancer controls and all
subjects, including brain, stomach and lung cancers (includes both non- and
current drinkers)
Number of alcoholic drinks per week
Subject
Mean Median
Minimum Maximum
s.d.
Breast Cases
2.6
2.0
0.0
7.0
2.1
Breast Controls
2.8
2.0
0.0
14.0
3.2
All
2.9
2.0
0.0
35.0
4.2
Subject
Breast Cases
Breast Controls
All
Number of units of alcohol per week
Mean Median
Minimum
5.3
3.6
0.0
5.9
3.0
0.0
5.7
3.0
0.0
44
Maximum
17.5
42.0
42.0
s.d.
5.0
8.3
8.1
Table 4.12 Average number of alcoholic drinks per week and average number of
units of alcohol per week for breast cancer cases, breast cancer controls and all
subjects (current drinkers only).
Number of alcoholic drinks per week
Subject
Mean Median
Minimum Maximum s.d.
Breast Cases
3.0
2.0
0.3
7.0
1.9
Breast Controls
3.9
3.0
0.3
14.0
3.1
All
3.9
2.5
0.3
35.0
4.4
Subject
Breast Cases
Breast Controls
All
Number of units of alcohol per week
Mean Median
Minimum
6.2
5.7
0.8
8.0
6.0
0.3
7.7
5.4
0.3
Maximum
17.5
42.0
42.0
s.d.
4.8
8.7
8.6
When restricted to only those who did drink (Table 4.12), it is apparent that breast cancer
controls consumed more alcoholic drinks and more units of alcohol per week than breast
cancer cases. The mean and median for both number of alcoholic drinks and units of
alcohol per week for breast cancer cases were also lower than all of the subjects together.
Three of the four brain cancer cases and four of the seven lung cancer cases drank alcohol.
One of the two stomach cancer cases drank 3 units of alcohol per week; the other stomach
cancer case did not drink.
4.11.1.7 Smoking
Current smokers were classified as having smoked at any time during the ten year period
before their qualification date and ex-smokers were classified as having stopped smoking at
some point before the ten years before their qualification date. All of the lung cancer and
stomach cancer cases were current smokers (Table 4.13). One respondent stated that they
were not a current smoker but did not state whether or not they were an ex-smoker.
Table 4.13 Smoking status of breast, lung, stomach and brain cancer cases and
breast cancer controls
Smoking Status
Subject
Current Smoker Ex-Smoker Never Smoker
Total
Breast Case
12
1
8
21
Breast Control
37
8
37
82
Brain Case
1
1
2
4
Stomach Case
2
0
0
2
Lung Case
7
0
0
7
Total
59
10
47
116
Among current smokers and ex-smokers the average age for starting to smoke was 17.8
years with a median age of 17 years. The ages reported ranged from 12.5 years old to 36
years old. Four proxies reported that they did not know the age at which the subject had
started to smoke.
The average number of cigarettes smoked per day by current smokers during the week was
14.6 cigarettes (median: 12.5 cigarettes) with a range of 2.5 cigarettes per day to 40
cigarettes per day. The average number of cigarettes smoked per day on the weekend was
15.7 cigarettes (median: 15 cigarettes) for current smokers with a range of 3 cigarettes per
day to 40 cigarettes per day.
The average number of pack years smoked, up to the qualifying date, for current smokers
was 20.7 years (median: 17.1 years) with a range of 0.5 pack-years to 77.2 pack years.
45
4.11.1.8 Reproductive and Family History
None of the 21 breast cancer cases reported having breast cancer before their work at
NSUK.
One case and one control had a mother with breast cancer; the case whose mother had
breast cancer was the case with no matched controls. Six controls and three cases had an
Aunt on their Mother’s side of the family with breast cancer and eleven controls and two
cases had a female sibling with breast cancer (Table 4.14).
Table 4.14 Family history of breast cancer for cases and controls.
Female Family Member with Breast Cancer
Mother Mother’s Sister Female Sibling
Yes
2
9
13
No
100
79
72
Don’t Know
2
2
1
Not Applicable
-14
18
Total
104
104
104
4.11.2 Case-Control Analysis
A number of hazards were considered for NSUK work. These are summarised and analysed
here for breast cancer, as this is the only cancer for which matched case-control recruitment
was carried out. There was one case recruited for whom no controls were found, and as this
person was excluded from the conditional logistic regression analyses they have not been
included in any descriptive tables given here. The hazards for the other cancers – brain,
stomach and lung – are summarised in Section 4.11.4.
Latency is defined as the delay between exposure to a disease-causing agent and the
appearance of manifestation of the disease. The analysis is constructed so that the
exposures in the period before cancer registration or death were excluded to allow for
latencies using periods of 5 and 10 years. Here we report the results for 10-year latency; the
results for both 5-year and no latency are shown in Appendix 1.
As described in Section 4.9 we considered whether people had ever been exposed to any of
the NSUK hazards as well as the duration of each exposure (based on the work history of
each subject and the exposure assessment). The difference in the number of people who had
ever worked in a fab area and those that had ever worked in a building containing a fab area
is due to the information being obtained from two differing sources (see Section 4.8.1.1 for
more detail).
For many of the hazards the median duration exposed for both cases and controls was zero
since less than half of the people were assessed as exposed at all.
Although the mean duration exposed to each hazard was generally higher for cases than
controls there were no large differences.
46
Table 4.15 Number of people ‘ever’ exposed to each hazard and the mean,
median and standard deviation duration exposed for cases and controls for a 10
year latency period
Case (n = 20)
Control (n = 83)
Ever
Med Mean
Max
SD Ever Med Mean
Max
NSUK hazards:
Acids
11.76 4.38 53
13
0.56
3.31
0.91 2.36 12.41
Solvents
9
0
1.02
0 0.78
4.58
11.00 2.54 40
Gases
10
0.00
1.25
7.67 2.18 34
0.00 0.62
6.21
Antimony trioxide
Arsenic and its
compounds
Carbon tetrachloride
Ceramic Fibre
Chromium Trioxide
and Chromic Acid
Trichloroethylene
Sulphuric Acid Mist
Ionising Radiation
Non-Ionising RF
Radiation
Non-Ionising UV
Radiation
Work in buildings
containing fab
areas
Work in fab areas
Night work
Rotational shifts
Circadian rhythm
disruption
Non-NSUK hazards
Night work
Rotational shifts
Circadian rhythm
disruption
Work at other
semiconductor mfr
plants
Employment Duration
Total*
NSUK
Non-NSUK
SD
3.08
1.21
1.25
8
0.00
0.84
5.28
1.74
30
0.00
0.55
12.41
1.55
8
0.00
0.99
6.67
2.00
28
0.00
0.45
6.21
1.01
3
3
0.00
0.00
0.16
0.09
1.50
1.00
0.45
0.25
10
8
0.00
0.00
0.08
0.05
2.44
0.76
0.30
0.16
6
0.00
0.45
7.37
1.60
22
0.00
0.16
2.41
0.37
1
12
0.00
0.07
0.07
2.79
1.50
11.21
0.33
4.08
4
51
0.00
0.67
0.06
1.73
2.25
12.41
0.32
2.63
5
0.00
0.48
4.48
1.21
20
0.00
0.31
4.55
0.80
7
0.00
0.96
7.37
1.93
28
0.00
0.41
6.07
0.91
14
2.06
3.39
11.76
4.07
57
1.25
2.85
12.41
3.33
12
0.30
3.01
13.16
4.30
48
1.00
3.44
14.38
4.52
14
2.39
3.68
13.16
4.57
54
1.25
3.68
14.38
4.46
9
5
0.00
0.00
1.42
0.06
6.38
4.66
2.12
1.34
35
9
0.00
0.00
1.88
0.44
14.38
10.38
3.16
1.62
9
0.00
1.42
6.38
2.12
35
0.00
1.88
14.38
3.16
0
1
0.00
0.00
0.00
0.02
0.00
0.50
0.00
0.11
11
16
0.00
0.00
0.66
0.96
12.00
16.18
2.09
2.68
1
0.00
0.02
0.50
0.11
18
0.00
1.24
16.18
3.11
1
0.00
0.02
0.34
0.07
3
0.00
0.18
10.00
1.19
24.74
3.23
10.00
22.28
5.19
11.49
36.61
13.16
23.50
9.87
4.89
6.07
24.27 21.97
3.38 4.66
9.00 10.35
35.53
18.92
27.93
9.27
4.74
6.66
*Total is time since leaving education and includes periods of unemployment
47
Subjects were asked if they were involved in any accidents/incidents where medical
attention was sought during their time at NSUK, meaning any accidents which had affected
them in some way. Very few people had been involved in incidents at NSUK (Table 4.16),
although a slightly higher proportion of cases had been involved in incidents involving acid
and gas liquid than controls.
Table 4.16 Number of people who had been involved in an incident involving
specific hazards, split by cases and controls
Case
Control
(n=20)
(n=83)
Acid
3
7
Gas
0
3
Gas Liquid
3
11
Radiation
0
1
As this was a matched case-control analysis, we carried out conditional logistic regressions
to assess whether any of the potential hazards were associated with whether a person was
diagnosed with breast cancer or not.
Table 4.17 shows the results of the separate conditional logistic regressions for the risk of
breast cancer for each of the lifestyle factors we considered. For some of these it was not
possible to estimate the odds ratio as none of the cases were exposed to the hazard.
None of the lifestyle factors shown in Table 4.17 were found to be statistically significant.
Alcohol consumption has recently been shown to be a risk factor for breast cancer25 but
here we found no evidence that it increased the risk of being diagnosed with breast cancer.
Table 4.17 Results of conditional logistic regressions for lifestyle factors. The table
shows the odds ratio of the risk of breast cancer (based on cancer registration) and
95% confidence interval for each.
Lifestyle
Odds ratio 95% Confidence Interval
Drinking Status
Current Drinker
1.92
0.53
6.88
Units Consumed per week
0.99
0.93
1.06
Smoking Status
Ex smoker
Current smoker
0.41
1.46
0.04
0.51
4.64
4.16
Cigarettes per day
0.91
0.79
1.05
Pack Years
0.99
0.95
1.03
House Type (ref: Flat, maisonette or apartment)
Whole house or bungalow
2.24
0.69
7.25
House ownership (ref: owned)
Rented
2.77
0.97
7.96
Education level attained (ref: none)
Higher and Further education qualifications
School education qualifications
1.43
0.51
0.35
0.11
5.95
2.25
Sister with breast cancer
0.36
0.04
3.61
Aunt (mother’s sister) with breast cancer
1.73
0.40
7.47
48
Table 4.18 shows the results of the conditional logistic regressions for NSUK hazards
which compare the exposed with those not exposed for a 10-year latency period
(corresponding tables for no latency and 5-year latency are given in Appendix 1). Whether
or not a person was exposed did not have any effect on whether a person was diagnosed
with breast cancer: none of the hazards were significant.
Table 4.18 Results of conditional logistic regressions for ever/never exposed
factors, for a 10 year latency period. The table shows the odds ratio of the risk of
breast cancer (based on cancer registration) and 95% confidence interval for each
Ever Exposed vs. Never exposed
Odds Ratio
95% Confidence Interval
Acid
1.05
0.30
3.65
Solvent
0.86
0.31
2.35
Gases
1.48
0.51
4.28
Antimony trioxide
Arsenic and its compounds
Carbon tetrachloride
Ceramic Fibre
Chromium
Trichloroethylene
Sulphuric Acid Mist
1.15
1.28
1.30
1.60
1.16
1.04
0.92
0.43
0.47
0.33
0.37
0.41
0.12
0.30
3.11
3.52
5.17
6.99
3.30
9.37
2.80
Ionising Radiation
Non-Ionising RF Radiation
Non-Ionising UV Radiation
1.04
1.02
1.10
0.34
0.36
0.30
3.22
2.90
4.09
Building
Fab
1.10
1.35
0.34
0.38
3.56
4.84
Nightshift
Rotational
Circadian
1.15
1.92
1.15
0.38
0.53
0.38
3.46
6.91
3.46
Non-NSUK
Nightshift*
Rotational
Circadian
Other Semi
0.17
0.15
1.56
0.02
0.02
0.14
1.59
1.36
17.75
0.38
0.59
4.21
8.85
Incidents
Gas Liquid
1.26
Acid
2.29
Gas*
Radiation*
*Odds ratios could not to be calculated for these hazards
49
While the dichotomy of ever-exposed versus never-exposed gives an impression of the
effects of hazards, a suitable ordinal or continuous measure of the exposure can be used to
give an indication of any dose-response effect. Here the measure used is duration exposed
(in years). Table 4.19 shows the results of the matched case-control analysis for duration of
exposure to each hazard, with a 10-year latency period. We also show the results for the
analysis based on the log of the duration exposed. Again the corresponding tables for no
latency and 5-year latency are shown in Appendix 1.
Duration of exposure was not found to have a significant effect on the risk of being
diagnosed with breast cancer for any of the hazards considered based on duration or the log
of duration.
When accounting for 10-year latency, none of the hazards were found to be associated with
an increased risk of breast cancer (Table 4.19). Additionally, these hazards were not found
to be significant in the analysis based on the log of duration, regardless of the latency
period.
With no adjustment for latency, however, associations between the risk of being diagnosed
with breast cancer and duration of exposure were statistically significant for some of the
hazards (see Appendix 1): in particular, exposure to sulphuric acid mist (95% CI: 1.02,
1.26), arsenic and its compounds (95% CI: 1.04, 1.59), gases (95% CI: 1.05, 1.60) and
acids (95% CI: 1.00, 1.24).
The regressions for each of the hazards were also carried out with adjustment for smoking
and drinking. However, the addition of these factors did not change the coefficients for the
hazards, or those for smoking and drinking, and so have not been reported here.
50
Table 4.19 Results of conditional logistic regressions for duration exposed to each
of the hazards, with a 10 year latency period, as well as for the log of the duration
exposed. The table shows the odds ratio of the risk of breast cancer (based on
cancer registration) and 95% confidence interval for each.
Duration Exposed
Duration Exposed Logged
Odds 95% Confidence
Odds
95% Confidence
Ratio
Interval
Ratio
Interval
Acid
1.10
0.93
1.30
0.99
0.75
1.31
1.10
0.81
1.51
0.85
0.62
1.16
Solvent
Gases
1.32
0.96
1.80
1.19
0.88
1.62
Antimony trioxide
Arsenic and its compounds
Carbon tetrachloride
Ceramic Fibre
Chromium
Trichloroethylene
Sulphuric Acid Mist
1.11
1.32
1.82
3.10
1.44
1.10
1.14
0.86
0.96
0.58
0.29
0.77
0.27
0.97
1.44
1.83
5.72
32.52
2.73
4.49
1.33
1.08
1.12
1.24
1.30
1.07
1.04
1.03
0.79
0.82
0.76
0.70
0.70
0.54
0.78
1.46
1.54
2.01
2.41
1.64
2.03
1.37
Ionising Radiation
Non-Ionising RF Radiation
Non-Ionising UV Radiation
1.21
1.63
1.06
0.76
0.96
0.90
1.91
2.75
1.24
1.02
1.12
0.99
0.72
0.80
0.73
1.45
1.56
1.33
Building
Fab
0.98
0.99
0.86
0.87
1.11
1.13
0.98
1.00
0.76
0.77
1.25
1.30
Nightshift
Rotational
Circadian
0.93
1.07
0.93
0.77
0.81
0.77
1.13
1.40
1.13
1.00
1.22
1.00
0.78
0.90
0.78
1.29
1.64
1.29
Non-NSUK
Nightshift*
Rotational
Circadian
Other Semi
0.25
0.24
0.67
0.02
0.02
0.11
2.80
2.83
4.26
0.56
0.55
0.91
0.27
0.27
0.41
1.14
1.10
2.00
Employment
Total#
1.02
0.90
1.16
NSUK
1.03
0.91
1.17
Non-NSUK
1.04
0.95
1.14
*Odds ratios could not be calculated for these hazards
5.10
1.75
1.39
0.46
0.76
0.68
56.87
4.03
2.82
#Total is time since leaving education and includes periods of unemployment
Figures 4.2 to 4.9 show the geometric mean exposure of the whole case-control set against
the ratio of the geometric mean of the controls to the exposure of the case, as described in
4.10.4. These graphs contain a considerable amount of information. We take as an
example the first graph in Figure 4.2, for duration of exposure to acids. The box-plot at the
top of the graph shows that, after omitting the 10-year latency period before the case
definition date, the duration metric spanned 2 orders of magnitude, from 0.1 to 10 years.
Comparing the data points to the diagonal dashed lines, it is evident that the distribution of
the cases’ durations also lay between 0.1 and 10 years. Finally, the box-plot to the right of
the graph shows the distribution of the ratios of the case’s exposure to the geometric mean
of the exposures of the corresponding controls. These ratios are approximations to withinset relative risks, and they are distributed close to symmetrically (on the log scale) around
51
the value of 1. The shape of the box-plot thus suggests that there was no excess risk of
breast cancer associated with duration of exposure to acids (after allowance for latency).
Examination of the remaining graphs shows that, for the majority of hazards considered,
the geometric mean exposure of the whole case-control set was low (below 1 year) for all
of the exposures with the exception of acids, sulphuric acid mist, non-ionising radiation
UV, fab work, and, working in a building where a fab was situated. These hazards had a
distribution of exposure duration scattered about 1 year. For all the hazards, the distribution
of case:control ratios was scattered around a central value of 1, again suggesting that the
hazards had no effect on the risk of breast cancer.
The plots also show the most influential points, defined here as where the deletion residuals
are more than 20% of the standard error. As expected, the influential points occurred where
the duration of exposure of the case was high, relative to their controls or where the
exposure of the control set was high, relative to the exposure of the case. Apart from this,
there was no systematic pattern evident from the influence statistics that implies that there
was any need to adjust for them. This was primarily because the graphs (and the associated
analyses) show no evidence of associations between breast cancer risk and exposure: if
there had been evidence of an association, it would have been of interest to investigate
whether that evidence was concentrated in a small subset of case-control sets.
52
Figure 4.2: Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Acids (left); Solvents (centre); Gases (right). Durations are adjusted for a 10 year latency period.
The solid upward pointing triangles (▲) are influential cases, while the solid downward pointing triangles (▼) are influential cases where one of
their controls is also influential
Solvents
0
=1
x ca
0.01
Geometric mean exposure of
case-control set (years)
53
.1
0.1
=0
x ca
Ratio of case exposure to controls' geometric mean
=1
x ca
0.1
1
10
1
.0
1
10
=0
x ca
1
0.1
.
=0
x ca
0.01
1
Geometric mean exposure of
case-control set (years)
.0
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
1
100
00
0
1
.0
0.1
=0
x ca
0.01
10
0
=1
x ca
=1
x ca
0.1
100
=1
x ca
00
1
Gases
00
=1
x ca
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
=0
x ca
Ratio of case exposure to controls' geometric mean
Acids
1
10
Geometric mean exposure of
case-control set (years)
Figure 4.3 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Arsenic and its compouds (left); Antimony trioxide (centre); Carbon tetrachloride (right).
Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲) are influential cases, while the solid downward
pointing triangles (▼) are influential cases where one of their controls is also influential
00
=1
x ca
0
=1
x ca
0.01
0.1
Geometric mean exposure of
case-control set (years)
54
.1
Ratio of case exposure to controls' geometric mean
=1
x ca
0.1
=0
x ca
10
1
1
.1
1
10
.0
1
.0
0.1
100
=0
x ca
0.01
=0
x ca
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
0
0
=0
x ca
1
.0
0.1
Geometric mean exposure of
case-control set (years)
1
=1
x ca
=1
x ca
0.1
10
00
00
1
100
=1
x ca
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
0.01
Carbon Tetrachloride
Antimony Trioxide
=0
x ca
Ratio of case exposure to controls' geometric mean
Arsenic
1
10
Geometric mean exposure of
case-control set (years)
Figure 4.4 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Ceramic fibre (left); Chromium Trioxide and Chromic Acid (centre-left); Sulphuric acid mist
(centre-right); Trichloroethylene (right). Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲) are
influential cases, while the solid downward pointing triangles (▼) are influential cases where one of their controls is also influential
55
0.1
1
10
1
Geometric mean exposure of
case-control set (years)
0.01
.
=0
x ca
10
0.1
1
.0
=0
x ca
Geometric mean exposure of
case-control set (years)
1
1
0.1
1
=1
x ca
=1
x ca
0.01
10
0
=1
x ca
0
=1
x ca
0.1
Ratio of case exposure to controls' geometric mean
1
100
00
=1
x ca
10
.
=0
x ca
10
100
1
.0
=0
x ca
1
1
0.1
.
=0
x ca
Geometric mean exposure of
case-control set (years)
0.01
1
.0
=0
x ca
10
1
1
0.1
=1
x ca
=1
x ca
0.1
.
=0
x ca
0.01
0
=1
x ca
0
=1
x ca
0.1
1
Trichloroethylene
00
=1
x ca
1
10
00
=1
x ca
00
=1
x ca
10
100
Sulphuric Acid Mist
Ratio of case exposure to controls' geometric mean
100
Ratio of case exposure to controls' geometric mean
Chromium Trioxide and Chromic Acid
1
.0
=0
x ca
Ratio of case exposure to controls' geometric mean
Ceramic Fibre
Geometric mean exposure of
case-control set (years)
Figure 4.5 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Ionising radiation (left); Non-ionising radiation Radio Frequency (centre); Non-ionising radiation
Ultra-Violet (right). Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲) are influential cases, while the
solid downward pointing triangles (▼) are influential cases where one of their controls is also influential
Non-Ionising RF Radiation
00
=1
x ca
0
0.1
=1
x ca
0.01
Geometric mean exposure of
case-control set (years)
56
.1
0.1
=0
x ca
Ratio of case exposure to controls' geometric mean
=1
x ca
1
1
10
10
.0
.1
1
100
=0
x ca
1
0.1
=0
x ca
0.01
.0
Geometric mean exposure of
case-control set (years)
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
1
0
0
1
.0
0.1
=0
x ca
0.01
10
=1
x ca
=1
x ca
0.1
100
00
00
1
Non-Ionising UV Radiation
=1
x ca
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
=0
x ca
Ratio of case exposure to controls' geometric mean
Ionising Radiation
1
10
Geometric mean exposure of
case-control set (years)
Figure 4.6 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Work in fab (left); Work in a building in which fab was situated (centre); Work in other semiconductor factory (right). Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲) are influential cases,
while the solid downward pointing triangles (▼) are influential cases where one of their controls is also influential
Work in Building in which Fab situated
00
1
=1
x ca
0
0.1
=1
x ca
0.01
Geometric mean exposure of
case-control set (years)
57
.1
0.1
=0
x ca
Ratio of case exposure to controls' geometric mean
=1
x ca
10
1
10
100
.0
.1
1
Work at other Semiconductor manufacturer
=0
x ca
1
0.1
=0
x ca
0.01
.0
Geometric mean exposure of
case-control set (years)
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
0
0
1
.0
0.1
=0
x ca
0.01
1
=1
x ca
=1
x ca
0.1
10
00
00
1
100
=1
x ca
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
=0
x ca
Ratio of case exposure to controls' geometric mean
Work in Fab
1
10
Geometric mean exposure of
case-control set (years)
Figure 4.7 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Nightshift (left); Rotational shift (centre); Circadian shift (right). Durations are adjusted for a 10
year latency period. The solid upward pointing triangles (▲) are influential cases, while the solid downward pointing triangles (▼) are influential
cases where one of their controls is also influential
00
=1
x ca
0
=1
x ca
0.01
0.1
Geometric mean exposure of
case-control set (years)
58
.1
Ratio of case exposure to controls' geometric mean
=1
x ca
0.1
=0
x ca
10
1
1
.1
1
10
.0
1
.0
0.1
100
=0
x ca
0.01
=0
x ca
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
0
0
=0
x ca
1
.0
0.1
Geometric mean exposure of
case-control set (years)
1
=1
x ca
=1
x ca
0.1
10
00
00
1
100
=1
x ca
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
0.01
Circadian Rhythm Disruption
Roatational Shifts
=0
x ca
Ratio of case exposure to controls' geometric mean
Night Work
1
10
Geometric mean exposure of
case-control set (years)
Figure 4.8 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Nightshift non-NSUK (left); Rotational shift non-NSUK (centre); Circadian shift non-NSUK (right).
Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲) are influential cases, while the solid downward
pointing triangles (▼) are influential cases where one of their controls is also influential
=1
x ca
0
=1
x ca
0.01
0.1
Geometric mean exposure of
case-control set (years)
59
.1
Ratio of case exposure to controls' geometric mean
00
0.1
=0
x ca
Ratio of case exposure to controls' geometric mean
=1
x ca
1
1
10
10
.0
.1
1
100
=0
x ca
1
0.1
=0
x ca
0.01
.0
Geometric mean exposure of
case-control set (years)
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
0
0
=0
x ca
1
.0
0.1
1
=1
x ca
=1
x ca
0.1
10
00
00
1
100
=1
x ca
=1
x ca
10
0.01
Non-NSUK Circadian Rhythm Disruption
Non-NSUK Rotational Shifts
100
=0
x ca
Ratio of case exposure to controls' geometric mean
Non-NSUK Night Work
1
10
Geometric mean exposure of
case-control set (years)
Figure 4.9 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Total duration of employment (left); Total duration of employment at NSUK (centre); Total
duration of employment outside of NSUK (right). Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲)
are influential cases, while the solid downward pointing triangles (▼) are influential cases where one of their controls is also influential
=1
x ca
00
=1
x ca
0
0.1
=1
x ca
0.01
60
.1
0.1
Geometric mean exposure of
case-control set (years)
=0
x ca
10
1
1
.1
1
10
.0
1
.0
0.1
100
=0
x ca
0.01
=0
x ca
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
Geometric mean exposure of
case-control set (years)
0
0
1
.0
0.1
=0
x ca
0.01
1
=1
x ca
=1
x ca
0.1
10
00
00
1
100
=1
x ca
=1
x ca
10
Employment Non-NSUK
Ratio of case exposure to controls' geometric mean
100
Ratio of case exposure to controls' geometric mean
Employment NSUK
=0
x ca
Ratio of case exposure to controls' geometric mean
Total Employment
1
10
Geometric mean exposure of
case-control set (years)
4.11.2.1 NON-NSUK work exposures
Table 4.20 shows the exposures for each of the hazards considered for work outside of NSUK
using the FINJEM database. Based on work histories very few people were actually exposed to
any of these hazards and as such none of them were found to have a significant effect on the risk
of developing breast cancer (Table 4.21).
Table 4.20 The mean, standard deviation (SD), geometric mean (GM) and geometric
standard deviation (GSD) of other occupational exposures outside of NSUK for cases
and controls
Case
Control
SD
GM GSD
Ever Mean SD
GM
GSD Ever Mean
Arsenic
0
0
(μg/m3)
Asbestos
5
18.23 53.38
0.04 51.26 20 16.28 44.19 0.04 46.90
(f/m3)
Aliphatic
hydrocarbon
1
3.24 14.84
0.01
7.98 5
44.60 296.40 0.01 14.85
solvents (ppm)
Aromatic
hydrocarbon
solvents (ppm)
Organic
Solvents
(ppm)
Ionising
Radiation
(mSv)
Non-Ionising
RF Radiation
(W/m2)
Non-Ionising
UV Radiation
(J/m2)
4
1.92
1
1
6.20
0.02
18.03 16
62.30
368.60
0.02 18.82
30.48 139.66
0.01
13.01
4
43.30
211.43
0.01 13.21
5.33
0.01
8.90
7
0.16
0.73
24.44
0
0
0
1
61
482.00 4388.00
0.01
4.54
0.01
5.73
Table 4.21 The conditional logistic regression results for occupational hazards outside
of NSUK. Results are shown for ever vs. never exposed, actual exposure and log of
exposure
Ever/Never
Exposure
Log of exposure
Hazard
Odds
95%
Odds
95%
Odds
95%
Ratio Confidence Ratio Confidence Ratio Confidence
Interval
Interval
Interval
3
Asbestos (f/m )
1.08
0.35
3.37
1.00 0.99 1.01
1.01 0.89 1.15
Aliphatic hydrocarbon
solvents (ppm)
0.81 0.09
7.61
1.00 0.98 1.01
0.97 0.78 1.20
Aromatic hydrocarbon
solvents (ppm)
0.79 0.22
2.83
1.00 0.97 1.02
1.03 0.88 1.22
Organic Solvents
(ppm)
1.05 0.10 10.59 1.00 1.00 1.00
1.00 0.83 1.22
Ionising radiation
(mSv)
1.02 0.75 1.38
0.32 0.04
2.63
1.05 0.92 1.20
Non-Ionising UV*
radiation (J/m2) *
1.00 0.56 1.78
*Odds ratios could not be calculated for these hazards
4.11.3 Subjects only Case-Control Analysis
As noted in Section 4.10.2 the more reliable information is likely to be that supplied by the
subjects themselves and so the same analysis was carried out with all of the proxies (and their
controls) removed. This resulted in a reduction of the number of case-control sets, from 20 to
13, as the majority of proxies were for cases.
Table 4.22 shows the descriptive statistics for this data set with a 10 year latency (0 and 5 year
latencies are shown in Appendix 1).
Removing the proxies resulted in the removal of many of the ‘never exposed’ cases and, in turn,
resulted in a higher mean duration exposed for each hazard. For the controls the same pattern
was evident for most, but not all, of the hazards.
Removing the proxies resulted in some differences between the cases and controls in terms of
the mean durations exposed to each hazard. Acid, gases, arsenic and its compounds, sulphuric
acid mist, and non-ionising radiation UV all had a difference of greater than 1 year of exposure
between the mean for cases and that of controls. The removal of the proxies also resulted in
slightly fewer controls having been involved in an incident at NSUK (Table 4.23).
None of the lifestyle factors considered were significant, with the exception of whether the
home was rented or owned. As none of the cases in this analysis were never-drinkers, an odds
ratio could not be calculated. Similarly, an odds ratio could not be calculated for whether any
sisters of the subject had had breast cancer or not.
62
Table 4.22 Number of people ‘ever’ exposed to each hazard and the mean, median
(med) and standard deviation (SD) duration exposed for cases and controls for a 10year latency period.
Case (n = 13)
Control (n = 51)
Ever Med Mean Max
SD Ever Med Mean Max
SD
Acid
8
2.61
4.23 11.76
4.94 32
1.25
2.54 12.14 3.17
Solvent
4
0.00
1.3 11.00
3.11 29
0.25
0.94
4.58 1.32
Gases
8
0.43
1.83
7.67
2.59 21
0.00
0.56
6.07 1.13
Antimony trioxide
Arsenic and its
compounds
Carbon
tetrachloride
Ceramic Fibre
Chromium
trioxide and
chromic acid
Trichloroethylene
Sulphuric acid
Mist
7
0.00
1.32
5.28
2.09
16
0.00
0.37
3.80
0.81
7
0.00
1.56
6.67
2.39
16
0.00
0.34
3.03
0.70
1
0.00
0.12
1.50
0.42
7
0.00
0.10
2.44
0.37
2
0.00
0.11
1.00
0.29
5
0.00
0.05
0.76
0.16
3
0.00
0.67
7.37
2.03
13
0.00
0.14
1.52
0.31
1
0.00
0.12
1.50
0.42
3
0.00
0.09
2.25
0.40
8
2.06
3.86
11.21
4.78
30
0.29
1.75
10.62
2.57
4
0.00
0.74
4.48
1.50
14
0.00
0.39
4.55
0.94
5
0.00
1.33
7.37
2.35
20
0.00
0.53
6.07
1.09
9
2.83
4.16
11.76
4.44
35
1.20
2.97
12.02
3.49
Building
Fab
8
8
2.61
2.61
3.77
4.20
13.16
13.16
4.94
5.23
31
35
0.80
1.63
3.87
4.12
14.38
14.38
4.87
4.81
Nightshift
Rotational
Circadian
6
3
6
0.00
0.00
0.00
1.68
0.62
1.68
6.38
4.66
6.38
2.43
1.46
2.43
19
3
19
0.00
0.00
0.00
1.95
0.27
1.95
14.38
10.38
14.38
3.49
1.47
3.49
Non-NSUK:
Nightshift
Rotational
Circadian
Other semi
0
1
1
0
0.00
0.00
0.00
0.00
0.00
0.04
0.04
0.00
0.00
0.50
0.50
0.00
0.00
0.14
0.14
0.00
7
10
12
2
0.00
0.00
0.00
0.00
0.70
0.81
1.20
0.20
12.00
12.00
12.00
10.00
2.29
2.28
2.95
1.39
21.77
6.38
9.59
21.15
6.52
9.46
36.61
13.16
23.50
9.81
5.23
5.41
22.07
3.38
8.86
19.19
4.70
9.95
Ionising Radiation
Non-Ionising RF
Radiation
Non-Ionising UV
Radiation
Employment duration
Total*
NSUK
Non-NSUK
*Total is time since leaving education and includes periods of unemployment
63
35.53 10.33
14.38 4.75
27.93 7.35
Table 4.23 Number of people who had been involved in an incident involving a number
of hazards, split by cases and controls
Hazard
Case
Control
Acid
3
5
Gas
0
2
Gas Liquid
3
7
Radiation
0
0
Table 4.24 Results of conditional logistic regressions for lifestyle factors. The table
shows the odds ratio of the risk of breast cancer (based on cancer registration) and
95% confidence interval for each. This information is for the dataset excluding proxy
case-control sets
Lifestyle
Odds
95%
ratio
Confidence
Interval
Drinking Status*
Current Drinker
Units Consumed per week
1.02
0.94
1.10
Smoking Status
Ex smoker
Current smoker
0.56
0.99
0.04
0.26
7.89
3.68
Cigarettes per day
0.92
0.75
1.14
Pack Years
0.98
0.93
1.04
House Type (ref: Flat, maisonette or apartment)
Whole house or bungalow
1.85
0.45
7.58
House ownership (ref: owned)
Rented
6.11
1.24
30.07
Education level attained (ref: none)
Higher and Further education qualifications
School education qualifications
0.50
0.58
0.05
0.10
5.21
3.25
0.84
0.09
7.51
Sister with breast cancer*
Aunt (mother’s sister) with breast cancer
*Odds ratios were unable to be calculated for these hazards
Table 4.25 shows that the odds ratio associated with solvents was low with 10 year latency
(95% CI: 0.06 to 0.97) and is statistically significant. This factor was also found to be
significant at 0 (95% CI: 0.06, 0.77) and 5 (95% CI: 0.07, 0.88) years latency (see Appendix 1).
64
Table 4.25 Results of conditional logistic regressions for ever/never exposed factors,
for a 10 year latency period. The table shows the odds ratio of the risk of breast cancer
(based on cancer registration) and 95% confidence interval for each. This information
is for the dataset excluding proxy case-control sets.
Ever Exposed vs. Never Exposed
Odds Ratio
0.87
0.31
3.03
Acid
Solvent
Gases
95% Confidence Interval
0.16
4.66
0.08
1.16
0.60
15.23
Antimony trioxide
Arsenic and its compounds
Carbon tetrachloride
Ceramic Fibre
Chromium
Trichloroethylene
Sulphuric Acid Mist
2.69
2.69
0.55
1.67
0.84
1.41
1.19
0.68
0.68
0.06
0.27
0.20
0.14
0.24
10.64
10.64
4.83
10.44
3.48
13.66
5.87
Ionising Radiation
Non-Ionising RF Radiation
Non-Ionising UV Radiation
1.17
0.94
1.22
0.32
0.26
0.18
4.26
3.36
8.12
Building
Fab
1.18
0.60
0.21
0.10
6.60
3.43
Nightshift
Rotational
Circadian
1.68
3.78
1.68
0.42
0.76
0.42
6.71
18.86
6.71
Non-NSUK
Nightshift*
Rotational
Circadian
Other Semi*
0.26
0.21
0.02
0.02
2.83
2.10
0.38
0.52
7.41
14.33
Incidents
Gas Liquid
1.69
Acid
2.72
Gas*
Radiation*
*Odds ratios could not be calculated for these hazards
65
Table 4.26 shows the regression results for all of the hazards with a 10-year latency period, with
results for no latency and 5-years given in Appendix 1. The statistically significant results are
shown in Table 4.27 for all three latency periods.
Table 4.26 Results of conditional logistic regressions for duration exposed to each of
the hazards, with a 10 year latency period, as well as for the log of the duration
exposed. The table shows the odds ratio of the risk of breast cancer (based on cancer
registration) and 95% confidence interval for each. This information is for the dataset
excluding proxy case-control sets
Duration Exposed
Duration Exposed Logged
Odds
95% Confidence
Odds
95% Confidence
Ratio
Interval
Ratio
Interval
Acid
1.23
0.96
1.57
1.09
0.73
1.65
Solvent
1.12
0.80
1.56
0.75
0.50
1.11
Gases
1.75
1.08
2.85
1.46
0.93
2.29
Antimony trioxide
Arsenic and its compounds
Carbon tetrachloride
Ceramic Fibre
Chromium
Trichloroethylene
Sulphuric Acid Mist
1.63
1.91
1.08
3.49
1.68
1.16
1.26
1.02
1.11
0.24
0.24
0.64
0.29
1.00
2.58
3.28
4.82
50.18
4.36
4.62
1.59
1.40
1.45
0.93
1.31
1.12
1.10
1.20
0.94
0.95
0.46
0.63
0.67
0.57
0.79
2.09
2.20
1.91
2.71
1.87
2.14
1.83
Ionising Radiation
Non-Ionising RF Radiation
Non-Ionising UV Radiation
1.25
1.56
1.15
0.78
0.90
0.91
2.00
2.70
1.46
1.06
1.07
1.14
0.72
0.73
0.71
1.56
1.58
1.83
Building
Fab
0.99
1.00
0.85
0.86
1.15
1.17
1.01
0.92
0.72
0.64
1.41
1.32
Nightshift
Rotational
Circadian
0.98
1.12
0.98
0.80
0.80
0.80
1.20
1.56
1.20
1.09
1.33
1.09
0.80
0.89
0.80
1.50
2.00
1.50
Non-NSUK
Nightshift*
Rotational
Circadian
Other Semi*
0.26
0.26
0.02
0.02
3.25
3.09
0.60
0.58
0.28
0.28
1.28
1.21
Employment
Total#
1.15
0.94
1.41
NSUK
1.17
0.94
1.45
Non-NSUK
0.98
0.88
1.09
*Odds ratios were unable to be calculated for these hazards
#Total is time since leaving education and includes periods of unemployment
Duration of exposure to arsenic and its compounds, gases, antimony trioxide, and sulphuric acid
mist were all found to have a significant effect on the risk of being diagnosed with breast cancer
even with 5-years and 10-years latency. However, there were no significant associations in the
66
analyses based on the log of the duration exposed for each of these hazards. Arsenic and its
compounds, gases, antimony trioxide and sulphuric acid were all highly correlated with each
other. Odds ratios and associated 95% confidence intervals these four hazards are shown with
and without adjustment for latency for the analysis based on duration of exposure in Table 4.27
and the log of the duration of exposure in Table 4.28.
The plots showing the most influential points when the proxies were removed are shown in
Appendix 1. As with the previous set of plots, the more influential points did not follow any
pattern and this suggests that no adjustment for such points was necessary.
Table 4.27 The significant conditional logistic regression results, shown for 0, 5 and 10
year latencies, for the duration of exposure. This information is for the dataset
excluding proxy case-control sets
Duration Exposed
0 years latency
5 years latency
10 years latency
Odds
95% CI
Odds
95% CI
Odds
95% CI
ratio
ratio
ratio
Arsenic
and its
compounds
1.63
1.10
2.42
1.60
1.08
2.39
1.91
1.11
3.28
Gases
1.49
1.07
2.09
1.51
1.06
2.15
1.75
1.08
2.85
Antimony
trioxide
1.47
1.07
2.01
1.45
1.03
2.04
1.63
1.02
2.58
Sulphuric
1.19
1.02
1.40
1.19
1.01
1.40
1.26
1.00
1.59
Acid Mist
Table 4.28 The significant conditional logistic regression results, shown for 0, 5 and 10
year latencies, for the log of the duration of exposure. This information is for the
dataset excluding proxy case-control sets
Log of Duration Exposed
0 years latency
5 years latency
10 years latency
Odds
95% CI
Odds
95% CI
Odds
95% CI
ratio
ratio
ratio
Arsenic
and its
comounds
1.34
0.95
1.88
1.38
0.96
1.98
1.45
0.95
2.20
1.25
0.88
1.77
1.31
0.90
1.90
1.46
0.93
2.29
Gases
Antimony
1.29
0.93
1.78
1.34
0.95
1.90
1.40
0.94
2.09
trioxide
Sulphuric
1.14
0.81
1.60
1.12
0.78
1.60
1.20
0.79
1.83
Acid Mist
67
4.11.3.1 Non-NSUK work
Removing the proxies resulted in fewer people being exposed to occupational hazards outside of
NSUK, and there was still no significant effect of any of these hazards on the risk of being
diagnosed with breast cancer.
Table 4.29 The mean, standard deviation (SD), geometric mean (GM) and geometric
standard deviation (GSD) of other occupational exposures outside of NSUK for cases
and controls. This information is shown for the dataset excluding all proxy case-control
sets.
Case
Control
Ever Mean
SD GM GSD Ever Mean
SD GM GSD
Arsenic
(μg/m3)
0
Asbestos
(f/m3)
3
3.71
7.96 0.03 32.75
10
12.37
Aliphatic
hydrocarbon
solvents
(ppm)
1
5.23
18.86 0.01 14.01
2
5.11
25.66 0.01
7.34
Aromatic
hydrocarbon
solvents
(ppm)
2
2.39
7.74 0.02 17.43
8
2.27
10.89 0.01
9.00
Organic
Solvents
(ppm)
1
49.23 177.50 0.01 26.10
2
48.12
Ionising
Radiation
(mSv)
1
4
0.21
NonIonising RF
Radiation
(W/m2)
Non-Ionising
UV Radiation
(J/m2)
0
8.62
31.06 0.01 16.09
37.41 0.03 34.92
241.49 0.01 11.38
0.90 0.01
4.87
0
0
0
1 784.00 5597.00 0.01
9.26
68
Table 4.30 The conditional logistic regression results for occupational hazards outside
of NSUK. Results are shown for ever vs. never exposed, actual exposure and log of
exposure. This information is shown for the dataset excluding all proxy case-control
sets.
Ever/Never Exposed
Duration of Exposure
Duration of exposure log
Odds
Ratio
95%
Confidence
Interval
Odds
Ratio
95%
Confidence
Interval
Asbestos
1.23
0.27
5.60
0.98
0.95
(f/m3)
Aliphatic
hydrocarbon
2.45
0.14 42.85
1.00
0.98
solvents
(ppm)
Aromatic
hydrocarbon
0.60
0.11
3.40
1.00
0.94
solvents
(ppm)
Organic
2.45
0.14 42.85
1.00
1.00
Solvents
(ppm)
Ionising
radiation
0.47
0.05
4.35
1.05
0.90
(mSv)
Non-ionising
1.00
0.56
UV radiation
(J/m2)*
*Odds Ratios were unable to be analysed for these hazards
95%
Confidence
Interval
Odds
Ratio
1.02
1.01
0.84
1.20
1.03
1.08
0.81
1.44
1.07
1.10
0.81
1.50
1.00
1.07
0.85
1.35
1.23
1.12
0.79
1.59
1.78
4.11.4 Case Series
The other cancers that were considered in this study were lung, stomach and brain, for which
only cases were recruited. All of these cancer cases were deceased at the time of the study and
so the information summarised here was obtained from proxies. It is likely that the information
provided by proxies was not as detailed as if the subject had provided it themselves as the proxy
would not necessarily know everything that their family member and/or colleague did during
their working day.
As there were no controls with which to make comparisons of assessed exposures of subjects
with these cancers, we have simply summarised the assessed exposures of cases based on
information provided about work at NSUK and elsewhere. It was not possible to formally
analyse the data for these subjects, especially as the number of cases was so small.
4.11.4.1 Lung Cancer
All 7 lung cancer cases were smokers, a known major risk factor for lung cancer.
All of the lung cancer cases were assessed as exposed to acids at the time of their diagnosis,
with 6 having exposure at 5 and 10 year latency. Similar patterns were seen for non-ionising
radiation UV and work in fab areas. The median durations of exposure for these and some of the
other hazards were high with no latency and decreased, as would be expected, with increasing
latency (Table 4.31).
69
Five of the lung cancer cases worked in diffusion and 2 in masking. For each subject only one
department was reported by the proxy. Looking at all those in the detailed study, it is clear that
diffusion, masking and deposition were the three most common departments, and for a number
of subjects – particularly for information provided by proxy – more than one of these
departments were listed together. Of the subjects in the detailed study, 81 were reported to have
worked in either masking, diffusion or deposition for some period during the time they worked
at NSUK (14 – deposition, 34 – diffusion, 32 – masking).
Five of the cases had family members who worked in ship-building, so there was also potential
for para-occupational exposure to asbestos.
With one exception, all cases of lung cancer had worked at NSUK for a period of at least 10
years prior to diagnosis, with half of these having left NSUK prior to diagnosis.
70
Table 4.31 The duration of NSUK exposures for all lung cancer cases for 0, 5 and 10
year latency
No latency
5 year latency
10 year latency
Ever Median Mean Ever Median Mean Ever Median Mean
Acid
7
9.83
8.81
6
6.59
7.00
6
3.26
4.98
Solvent
4
0.04
1.67
3
0.00
1.31
3
0.00
0.82
Gases
6
4.82
3.67
6
3.29
2.91
6
1.36
2.13
Antimony trioxide
Arsenic and its
compounds
Carbon
tetrachloride
Ceramic Fibre
Chromium
trioxide and
chromic acid
Trichloroethylene
Sulphuric acid mist
5
5
4.96
3.57
4.23
2.79
5
5
3.29
2.24
3.30
2.16
5
5
1.36
1.33
2.37
1.53
1
0.00
0.16
1
0.00
0.13
1
0.00
0.08
3
0.00
0.70
3
0.00
0.55
3
0.00
0.40
3
0.00
0.36
2
0.00
0.31
2
0.00
0.26
0
6
9.82
8.23
0
6
6.16
0.00
6.48
0
6
2.66
0.00
4.67
Ionising radiation
Non ionising
Radiation RF
Non ionising
Radiation UV
2
3
0.00
0.00
0.72
1.27
2
3
0.00
0.00
0.62
1.11
2
3
0.00
0.00
0.53
0.91
7
9.93
9.21
6
6.59
7.26
6
3.26
5.14
Fab
Building
7
4
14.89
4.00
13.64
8.72
7
4
9.88
4.00
11.03
6.82
6
4
4.88
4.00
8.16
4.68
Nightshift
Rotational
Circadian
4
2
4
0.07
0.00
0.07
6.31
0.30
6.31
3
1
3
0.00
0.00
0.00
5.36
0.29
5.36
3
1
3
0.00
0.00
0.00
4.28
0.29
4.28
Non-NSUK
Nightshift
Rotational
Circadian
Other Semi
0
2
2
1
0.00
0.00
0.00
0.76
0.76
0.14
0
2
2
1
0.00
0.00
0.00
0.76
0.76
0.14
0
2
2
1
0.00
0.00
0.00
0.76
0.76
0.14
31.40
4.89
18.08
32.36
8.16
16.21
Employment
Total*
41.40 39.26
36.40 35.93
NSUK
14.89 13.64
9.89
11.02
Non-NSUK
18.08 17.63
18.08 16.93
*Total is time since leaving education and includes periods of unemployment
Non-NSUK exposures
Of the occupational hazards assessed for work outside of NSUK only one person had an
exposure to asbestos, at 10 year latency, while another had an exposure to aromatic
hydrocarbons (Table 4.32).
71
Table 4.32 The exposures to hazards from work outside of NSUK (according to the
FINJEM) for all lung cancer cases
Ever
Median
Mean
SD
GM
GSD
0
Arsenic (μg/m3)
1
0.00
5.35
14.14
0.02 29.14
Asbestos (f/m3)
Aliphatic hydrocarbon
0
solvents (ppm)
Aromatic hydrocarbon
1
0.04
0.11
0.01
4.68
solvents (ppm)
Organic Solvents (ppm)
0
0
Ionising Radiation (mSv)
0
Non-Ionising RF Radiation
(W/m2)
Non-Ionising UV Radiation
0
(J/m2)
4.11.4.2 Brain Cancer
The proxy interviewees reported that all four brain cancer cases had worked in fab areas at some
time, which was not unusual and true of 85% of the individuals in the detailed study. Two of
these four had accrued employment time in fab areas prior to 10 years before diagnosis.
However, there was no assessed exposure to any of the chemical hazards based on reported job
histories, other than one case with exposure to solvents prior to 5 years before diagnosis. There
was no assessed exposure to ionising radiation prior to 10 years before diagnosis for any of the
cases. Work in maintenance was reported in only 1 case.
4.11.5 Stomach Cancer
As there were only two stomach cancer cases considered here it is difficult to draw any
conclusions. Both were working at NSUK at the time of diagnosis. Both had worked in testing
just prior to diagnosis, although one was for a relatively short period of time. Both had family
members working in shipbuilding. Both cases were assessed as exposed to acids, solvents and
non-ionising radiation UV at 0 and 5 years latency but neither were exposed to any of the
NSUK hazards at 10 year latency (Table 4.34). Only one of the cases had any exposure to the
hazards considered from work outside of NSUK (ionising radiation and aromatic hydrocarbon
solvents) (Table 4.35).
72
Table 4.33 The duration of NSUK exposures for all stomach cancer cases for 0, 5 and
10 year latency
No latency
5 year latency
10 year latency
Median Mean
Ever Median Mean Ever Median Mean Ever
Acid
2
2.70
2.70
2
1.09
1.09
0
Solvent
2
2.06 20.60 2
0.92
0.92
0
Gases
1
0.85
0.85
1
0.23
0.23
0
1
0.43
0.43
1
0.12
0.12
0
1
0.85
0.85
1
0.23
0.23
0
1
0.21
0.21
1
0.06
0.06
0
0
1
1.07
1.07
0
1
0.29
0.29
0
0
1
0.43
0.43
1
0.12
0.12
0
1
0.21
0.21
1
0.06
0.06
0
2
2.49
2.49
2
1.04
1.04
0
Fab
Building
1
1
2.38
1.04
2.38
1.04
1
0
0.52
0.52
0
0
Nightshift
Rotational
Circadian
1
1
1
1.25
1.25
1.25
1.25
1.25
1.25
1
1
1
0.26
0.26
0.26
0.26
0.26
0.26
0
0
0
Non-NSUK
Nightshift
Rotational
Circadian
Other semi
1
1
1
0
3.42
3.00
3.42
3.42
3.00
3.42
1
1
1
0
3.21
3.00
3.21
3.21
3.00
3.21
1
1
1
0
Antimony trioxide
Arsenic and its
compounds
Carbon tetrachloride
Ceramic fibre
Chromium
trioxide and
chromic acid
Trichloroethylene
Sulphuric acid mist
Ionising radiation
Non-ionising RF
radiation
Non-ionising UV
radiation
0
0
Employment
Total*
21.89 21.89
16.89
16.89
NSUK
7.88
7.88
2.94
2.94
Non-NSUK
8.00
8.00
8.00
8.00
*Total is time since leaving education and includes periods of unemployment
73
3.00
3.00
3.00
3.00
3.00
3.00
11.89
0.00
7.00
11.89
0.00
7.00
Table 4.34 The exposures to hazards from work outside of NSUK (according to the
FINJEM) for all stomach cancer cases.
Ever
0
0
0
1
0
1
0
0
Arsenic (μg/m3)
Asbestos (f/m3)
Aliphatic hydrocarbon solvents (ppm)
Aromatic hydrocarbon solvents (ppm)
Organic Solvents (ppm)
Ionising Radiation (mSv)
Non-Ionising RF Radiation (W/m2)
Non-Ionising UV Radiation (J/m2)
Mean
SD
GM
GSD
0.08
0.11
0.03
11.08
0.75
1.06
0.09
56.43
4.12 FALSE PROXIES: RECRUITMENT
In total, 11 false proxies were recruited and interviewed. Five were colleagues/friends of the
subject while the other 6 were family members.
4.12.1 Job History
Irrespective of whether the false proxy was a family member or colleague/friend, no job history
completely matched that given by the subject. Generally false proxies missed jobs which the
subject had noted, but in 4 cases the proxy actually listed jobs that the subject did not report.
The jobs that were given were generally in the right order with the exception of one of the cases.
Two of the colleague/friend false proxies were unable to give any detail of work outside of
NSUK. Family member false proxies gave more detail of jobs outside of NSUK, while the
colleague false proxy was able, in general, to give a bit more detail of work carried out within
NSUK.
Some employment dates were not given or only partially given. When the false proxy provided
dates, 6 out of 11 of them reported dates that were within two years of what was provided by the
subject. There was one false proxy who, although the total duration of employment in each job
was approximately correct, had reported dates about 10 years different to those reported by the
subject.
4.12.2 NSUK work history
None of the false proxies gave exactly the same information as their associated subject,
although a few were close. Generally, the false proxy gave a shorter list of processes than the
subject and did not list all buildings, departments and shift patterns noted by the subject.
The actual dates of working the different jobs/processes/shift patterns did not usually agree, but
the total time worked at NSUK was usually approximately correct.
The differences in information provided by the subjects and their false proxies resulted in
differences in assessed exposures to the hazards considered here, as these exposures were
derived from the processes listed in a person’s NSUK work history.
Table 4.36 shows those assigned as ever- and never-exposed, based on the job history reported
by both subject and false proxy. The agreement between these assigned exposures based on
false proxies and subjects was quite good. However, Figure 4.10 shows that there tended to be
74
an underestimate of exposure based on the information provided by false proxies. However, the
false proxies rarely identified a subject as being exposed to a hazard when the subject
themselves had not; this only happened in this sample for 1 subject-false proxy pair (for four of
the hazards). Also, for each of the hazards there were a number of pairs who were assigned as
exposed based on the subject history but not exposed based on information from the false proxy.
Table 4.35 Cross-tabulation of reports of whether each subject is assigned as being
exposed or not, by the subject and the false proxy
Arsenic and
Antimony
Solvents
Acids
Gases
its
trioxide
compounds
Proxy
Subject
No
Yes
No
Subject
Yes
Subject
No
Yes
No
5
4
Yes
0
2
Proxy
No
3
3
Proxy
Yes
0
5
No
5
1
Yes
0
5
Proxy
No
5
2
Proxy
Yes
1
3
No
6
1
Yes
1
3
Carbon
tetrachloride
Ceramic
fibre
Chromium
trioxide and
chromic acid
Sulphuric
acid mist
Trichloroethylene
Proxy
Proxy
Proxy
Proxy
Proxy
No
9
1
Yes
0
1
No
7
2
Yes
1
1
No
7
1
Yes
1
2
No
3
3
Ionising
radiation
Non ionising RF
radiation
Non ionising
UV radiation
Proxy
Proxy
Proxy
No
6
3
Yes
0
2
No
6
3
Yes
0
2
No
1
4
Yes
0
5
No
10
1
Yes
0
0
Yes
0
6
Figure 4.10 compares the estimated durations of exposure when obtained based on the subjects
information with those based on the false proxies’ information. The information provided by
false proxies generally led to a shorter average duration of exposure to each of the hazards than
that from subjects. However, in a few instances proxies provided information which yielded a
higher duration of exposure compared to their subjects.
Just over half of the durations of exposure were estimated to be zero, based on the information
provided by the subject and the false proxy. For about 50% of the remaining exposure durations
there was a difference of more than one year.
75
Figure 4.10 Comparisons of the estimated duration exposed to each hazard based on
the information provided by the subject and the false proxy
16
Solvents
Duation exposed based on False Proxy
Duation exposed based on False Proxy
4
3
2
1
0
Acids
14
12
10
8
6
4
2
0
0
1
2
3
4
0
Duration exposed based on Subject
Gases
Duation exposed based on False Proxy
Duation exposed based on False Proxy
4
6
8
10
12
14
16
Duration exposed based on Subject
6
6
2
5
4
3
2
1
Antimony
5
4
3
2
1
0
0
0
1
2
3
4
5
0
6
1
2
3
4
5
Duration exposed based on Subject
Duration exposed based on Subject
76
6
Figure 4.10 continued
2.5
Arsenic
Duation exposed based on False Proxy
Duation exposed based on False Proxy
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Carbon tetrachloride
2.0
1.5
1.0
0.5
0.0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0.0
Duration exposed based on Subject
1.0
Ceramic fibre
Duation exposed based on False Proxy
Duation exposed based on False Proxy
2.0
1.5
1.0
0.5
0.0
1.5
2.0
2.5
Chromium trioxide and chromic acid
0.8
0.6
0.4
0.2
0.5
1.0
1.5
0.0
2.0
0.2
0.4
0.6
0.8
1.0
Duration exposed based on Subject
Duration exposed based on Subject
1.0
Sulphuric acid mist
Duation exposed based on False Proxy
Duation exposed based on False Proxy
1.0
0.0
0.0
16
0.5
Duration exposed based on Subject
14
12
10
8
6
4
2
0
Trichloroethylene
0.8
0.6
0.4
0.2
0.0
0
2
4
6
8
10
12
14
16
0.0
Duration exposed based on Subject
0.2
0.4
0.6
0.8
Duration exposed based on Subject
77
1.0
Figure 4.10 continued
5
Ionising radiation
Duation exposed based on False Proxy
Duation exposed based on False Proxy
5
4
3
2
1
4
3
2
1
0
0
0
1
2
3
4
0
5
14
1
2
3
4
5
Duration exposed based on Subject
Duration exposed based on Subject
Duation exposed based on False Proxy
Non-ionising radio frequency radiation
Non-ionsing ultra violet radiation
12
10
8
6
4
2
0
0
2
4
6
8
10
12
14
Duration exposed based on Subject
4.12.3 Incidents and Family work
False proxies usually did not provide information about any incidents that the subject had at
work, and in the one case where they did give this information they were not able to supply the
same level of detail that the subject had.
Eight of the 11 false proxies gave details of hazardous jobs worked in by family members. Four
of these were approximately the same as reported by the subject, but the remaining four were
completely different. Three of the false proxies were not able to give any information at all.
None of the false proxies were able to give dates for the family members work history section.
4.12.4 Conclusions
In this limited assessment it is clear that false proxies provided less complete information than
subjects themselves. In the case of the overall job history this mainly consisted of missing dates:
the actual jobs reported by false proxies agreed closely with those supplied by the subject. The
78
false proxy was not particularly good at identifying family members who had worked in
hazardous jobs. The main differences, however, came when concentrating on the detailed work
history while employed at NSUK. The differences in processes, tasks and departments given
resulted in differences in the durations of exposure calculated.
If the findings of our limited assessment of the agreement between information provided by
proxies and subjects themselves are typical of proxies in general, it is likely that there will have
been at least some effect on analyses that include information derived from proxies. Therefore,
although removing proxies from the study reduces the number of case-control sets, it is likely to
give more reliable results.
There is an additional question about the reliability of proxy information when the proxy is for a
subject who thought that their cancer was caused by their work. In this situation the proxy could
know more about the subject’s work than the false proxies in our small evaluation study. If
someone believed that their cancer was caused by something that they did or were in contact
with at work, they may be more likely to discuss what their work with family members and/or
colleagues. This would result in the proxy having more information than they would normally
have had. Although this would mean that the information provided could be more reliable than
was our experience of the false proxies here, it may result in the information being more biased
towards what the subject thought was the cause of their illness.
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5 DISCUSSION 5.1
BACKGROUND
The overall aim of this study was to help clarify whether rates of female lung, stomach and
breast cancer, and of male brain cancer in the NSUK workforce might be related to work done
at the Greenock plant. It was carried out in response to the recommendation from the report on
the earlier cohort mortality and cancer incidence study at NSUK that a plant-based case-control
study should be carried out to investigate, as far as possible, whether some cases of certain
cancer types might be work-related1. It was recommended that historical exposures of cases of
selected cancer types and suitably chosen controls should be examined, including an in-depth
assessment of past occupational exposures to known or suspected carcinogens, together with
such assessments as would be possible of other relevant risk factors (e.g. lifestyle, familial
history, etc.).
The earlier report recommended that the primary focus of a case-control study should be on
lung and stomach cancer (both sexes), but that female breast cancer and brain cancer in males
should be examined at the same time as this was being done. The report also recommended that
case ascertainment for the original cohort study should be kept open in order that further
examination of the cancer mortality and incidence of those workers could be made at an
appropriate point in the future when the mean length of follow-up was suitably increased. An
update of the original cohort analysis was incorporated as an objective of the present study
during the course of developing the protocol because it became clear that the time elapsed since
the original analysis would be sufficient for an update to provide further useful information in
pursuit of the overall study aim.
Following discussion with NSUK and its advisers, and the independent Scientific Steering
Committee established for the original cohort study, a decision was taken to use the case-control
approach for lung and breast cancer only, restricting further study of stomach and brain cancer
to examination of the work and lifestyle histories of the cases only. This was because the
numbers of cases of these two cancers were too small for a case-control study. Although the
study of cases only was always less likely to provide conclusive results than comparisons of
cases and controls, we judged that this could still potentially provide useful information in
support of the overall study aim. For example, if it were possible to rule out that cases had
common exposure patterns at NSUK this would tend to argue against a cause linked to work at
the plant. Because of the small numbers of male lung and stomach cancers and the overall
differences between the incidences of these cancers in males and females a decision was also
made to study only female cases of these two cancers.
All of the lung cancer cases available for inclusion in the case-control study were deceased so
the researchers approached close relatives or workmates, seeking their help as proxy
interviewees; fewer than half of those contacted felt able to help the study in this way. The final
response rate for breast cancer cases was 53% and in the light of this and the low response rate
for lung cancer careful consideration was given (including seeking advice from the Scientific
Steering Committee) to abandoning the further investigation of possible work and other factors.
On purely scientific grounds such a decision was considered justifiable, but HSE decided that it
should meet the commitment it had made to the workforce at NSUK to investigate the early
findings as carefully as possible. However, a decision was taken to abandon the formal casecontrol analysis of lung cancer in favour of a case-only assessment along the lines of that
planned for female stomach cancer and male brain cancer. Changes to the original intentions of
the study, and their implication for the value of its outcomes were communicated to the
workforce when these decisions were made.
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5.2
FINDINGS
A key issue to keep in mind when considering our updated findings is the small size of the study
on which they are based. Study size is important since it has a direct bearing on the amount of
the uncertainty in the results, and hence the ability of a study to identify associations of concern.
Care is needed in interpreting negative findings (ie those which do no provide evidence of an
increased risk or of associations between exposure and disease) since the absence of evidence of
an association does not amount to positive evidence of no association. Thus even with large
studies it will not usually be possibly to entirely rule out any associations between exposure and
disease. Given the small size of our study, many of the SMRs and SRRs in the cohort update
and ORs in the breast cancer case-control analyses have wide confidence limits indicating that a
wide range of values would be consistent statistically with the data as observed. In this context
it is important not to overplay the absence of a statistically significant association. On the other
hand the likelihood of observing false-positive findings (results which are declared as being
statistically significant which in fact are due to chance alone) is increased in our study due to the
large number of outcomes and exposures considered. These issues were taken into account
when considering the value of a follow-up study. The possibility of an inconclusive outcome
was explained to the workforce and it was agreed that the study should proceed.
5.2.1
Overall mortality and cancer incidence
The overall pattern of mortality and cancer incidence was similar in the updated cohort analysis
to that seen originally: a substantial deficit of deaths from all causes among men, a less
substantial deficit among women, but numbers of registrations of cancer (all malignant
neoplasms) consistent with expectation for both men and women. Among men, deficits of
mortality were seen in all three of the major disease groups considered – all malignant
neoplasms, circulatory disease and respiratory disease – whereas among women, mortality from
all malignant neoplasms and respiratory disease was consistent with expectations. These
different patterns for men and women may to some extent reflect differing characteristics of
male and female workers: for example, it is likely that a higher proportion of male workers
originated from outside the local area.
The findings are also suggestive of a healthy worker effect (HWE). This is a general tendency
for working populations to suffer lower disease rates than the population as a whole. This
occurs because people in work are by definition healthy enough to hold a job, while the
population as a whole contains people who are not. As a consequence, working populations tend
to record lower than average mortality. The HWE is strongest in current workers: a cohort who
started as current workers will gradually lose their healthy worker advantage and their average
health status will tend towards that of the general population. It would therefore not be
surprising to see fewer deaths overall than expected based on observations arising within the
first ten years from workers’ employment start dates. However, we found similar deficits among
those with more than 10 years since first employment as well as among those with less than 10
years since first employment, which is more unusual. The HWE is usually most marked for
circulatory and respiratory diseases, and has a more limited impact on cancer, whereas in our
study we saw deficits of mortality among men due to all three of these disease groups. Among
women, we observed a deficit of mortality from circulatory diseases only.
Another possible explanation for a deficit in overall mortality is an under-ascertainment of
deaths due to losses to follow-up or errors in tracing individuals against the central NHS
register. However, the fact that numbers of observed cancer registrations overall (and cancer
deaths among women) were consistent with expected numbers tends to argue against this, and
we conclude that these factors are not likely to be a source of bias in the study.
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5.2.2
Specific cancer sites
In the updated cohort analysis, none of the specific cancer site groups identified for study at the
outset showed observed numbers of cancer registrations among men that were statistically
significantly different from expectation. Among women, the only group for which there were
significantly more cancer registrations than expected was for stomach cancer, but this finding
was of borderline statistical significance, and only when including both registrations in one
individual.
5.2.3
Breast cancer
The findings of the updated cohort analysis in relation to female breast cancer are consistent
with those of the original study. The overall breast cancer SRR was slightly lower than that seen
originally. As before, there were more cancer registrations than expected, but not statistically
significantly so. With time since first employment restricted to less than 10 years we did
observe excesses among those aged 50 years or more and among those employed from 1982
onwards. For these results to be consistent with a workplace cause it would have had to lead to
cancer within 10 years of exposure, and this is unlikely given the usual latency of solid tumours.
In addition to the fact that the various analyses we carried out in the breast cancer case-control
study were based on a small numbers subjects, it is also important to note that those included
were a subset of the total number of eligible cases invited to participate (50%, or less for some
analyses). In itself, the small number of cases limited the statistical power of the analyses, but
the fact that a substantial number of cases could not be included also raises the possibility of
non-response bias which could have occurred if participating cases were not representative of
eligible cases in general. Therefore, any conclusions drawn from these analyses should be
regarded as tentative.
Any evidence for associations between increased breast cancer risk and NSUK-hazards was
considered by carrying out a number of different analyses. We considered exposures occurring
at any time before diagnosis or just those that took place prior to 10 years before this; analyses
based on all cases and controls and those where just the subjects themselves provided the
response (i.e. excluding subjects for whom proxies responded); and we assessed exposures on a
simple ever- or never-exposed basis, as well as using duration or log-duration of exposure.
Some associations between increased breast cancer risk and certain hazards were evident in
some of these analyses. In particular, duration of exposure prior to 10 years before diagnosis to
the general category toxic gases and to the specific agents arsenic and its compounds, antimony
trioxide, and sulphuric acid mist were associated with an increased likelihood of being a breast
cancer case in the analysis restricted to subject-only responses. However, there were no
statistically significant associations for these hazards in the analyses based on the log-duration
of exposure or an ever/never-exposed assessment. In general, we found no evidence of an
association between an increased likelihood of breast cancer and any of the lifestyle factors or
non-NSUK workplace hazards we considered. The only exception was living in rented
accommodation, where a statistically significant positive association was found in the analysis
restricted to subject-only responses.
There is no clear way of deciding how much weight to place on the different analyses of NSUK
hazards in interpreting whether these results amount to evidence of an association between
exposure to certain toxic gases, or to arsenic and its compounds, antimony trioxide, and
sulphuric acid mist and an increased breast cancer risk. There may be some grounds for
regarding the analyses based on subject only responses as more reliable even though they were
based on smaller numbers (as mentioned in section 4 and discussed later). The analyses based
on duration of exposure and log-duration of exposure test for different mathematical forms of
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any relationship with breast cancer risk, and there is no strong reason for preferring one of these
analyses to the other. Thus we cannot rule out an association on the grounds that the results of
the latter were not statistically significant. On the other hand, it is likely that an important
association would be evident in all three types of analysis – those based on an ever/never
assessment, duration of exposure, and log duration of exposure – but this was not the case here.
Other important considerations in interpreting these results are the high degree of correlation
between those exposed to different hazards, the large number of statistical tests implicit in these
analyses (leading to an increased likelihood of some results being declared statistically
significant by chance alone) and whether other studies have also shown associations with these
same hazards.
We were not able to carry out exposure assessments for each individual agent within the
grouped categories of key substances (solvents, acids and toxic gases). This means it was not
possible to determine whether the association seen with duration of exposure to toxic gases was
because exposure to one or more of the specific substances categorised as such (including
arsine, phosphine, boron trichloride, silane, dichlorosilane, hydrogen chloride, silicon
tetrachloride) was more common among cases than the controls. Most of those exposed to toxic
gases were also exposed to arsenic and its compounds and antimony trioxide and so an apparent
association with toxic gases in general could simply reflect associations seen in some of our
analyses for these specific substances. Arsine can be regarded as equivalent to arsenic in terms
of carcinogenicity given its metabolism to other arsenic compounds. Reference to the
International Agency for Research on Cancer (IARC) monographs and a search of the
“PubMed” literature database revealed no substantive evidence in humans on the potential
carcinogenicity of phosphine, boron tetrachloride, silane, dichlorosilane, hydrogen chloride, or
silicon tetrachloride, all of which have acute toxic effects likely to limit chronic exposure.
There was a high degree of correlation between the duration of exposure to each of the three
specific substances for which associations were seen in some of our analyses: antimony
trioxide, arsenic and its compounds, and sulphuric acid mist. For example, in the subject-only
analysis, all seven cases exposed to antimony trioxide were also exposed to arsenic and its
compounds and to sulphuric acid mist. An association seen in respect of one of these substances
thus tends to result in associations being evident for the others. This makes it difficult to
distinguish which exposures might point towards any real effect if any such effect existed. Both
arsenic and sulphuric acid mists have been classified as established (category 1) carcinogens by
the IARC based on evidence of causal associations between exposure and certain cancer
sites26,27, though not breast cancer. Despite fairly extensive study, the breast has not been
identified as a potential cancer site in respect of these substances. In a recent review of the
epidemiological evidence for the carcinogenicity of arsenic in humans by IARC, breast cancer
was not among those cancer sites for which it was concluded that arsenic is an established cause
(lung, skin and urinary bladder), nor was it among those sites for which there was some
evidence of a more limited nature (kidney, liver and prostate)28. The effects of exposure to
antimony trioxide in humans have not been studied as extensively as arsenic. Those studies that
are available have been of populations composed mainly of male workers, and it is not clear
whether observations of increased risks of lung cancer could be explained by co-exposures such
as smoking, arsenic, or PAHs29. Antimony trioxide is currently classified as a possible (category
2B) carcinogen by IARC based on evidence that it causes lung cancer in animal studies, but
inconclusive evidence from human epidemiology.
Taking into account all these considerations, we think it is unlikely that exposure to arsenic and
its compounds, antimony trioxide, or sulphuric acid mist during the course of work at NSUK
has led to an increased risk of breast cancer, and that the apparent associations seen in some of
our analyses are more likely to have occurred due to chance.
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Breast cancer was selected as one of the groups for study in the original investigation because it
was of concern to Phase Two and because of a potential for exposure to ionising radiation at
NSUK, an established risk factor. At the time the results of the initial study were published
some evidence was beginning to emerge that breast cancer might be associated with shift
work30,31,32. IARC recently reviewed this and more recent evidence and concluded that shiftwork
that involves circadian disruption is probably carcinogenic to humans18. In this case-control
analysis we observed no association between breast cancer risk and exposure to ionising
radiation or shift/night work, either at the plant or elsewhere.
5.2.4
Lung cancer
The previous analysis of the cohort revealed 11 lung cancer registrations among women, nearly
3 times the number expected and a finding that was statistically significant. There were only 2
registrations among men, fewer than expected – though not statistically significantly so. Six of
the female registrations in this earlier analysis occurred more than 10 years after the start of
employment. All 6 of these women started work at the plant before 1982 and this amounted to
nearly three times the number of expected lung cancer deaths in this subgroup, though this
finding was of borderline statistical significance due the small numbers. We concluded that the
overall excess and, in particular the excess seen with time since first employment restricted to
10 years or more might be indicative of a cause arising from work at NSUK.
Although there were 5 additional lung cancer registrations among women in the updated
analysis, the total of 16 did not amount to a statistically significant excess over expectation after
accounting for the further 8 years of follow-up. There was no longer any excess of registrations
with time since first employment restricted to 10 years or more, either overall or among those
employed before 1982. With time since first employment restricted to less than 10 years we did
see excesses of female lung cancers among those first employed in 1982 or later, and among
those classified as fab workers. For these results to be consistent with a workplace cause
affecting those employed in more recent times, such a cause would have to lead to cancer within
10 years of exposure, which again is unlikely given the usual latency of solid tumours. The
analyses of lung cancer registrations in relation to duration of employment did not provide any
further evidence for a workplace cause.
Detailed study of the 7 lung cancers in the case series led to no positive evidence of a workplace
cause of lung cancer such as might have been arguable if, for example, a number of the cases
had occurred in non-smokers with common occupational exposure patterns. Although all 7
cases accrued at least some exposure time for many of the hazards at NSUK – with 6 accruing
some exposure prior to 10 years before diagnosis – all 7 individuals were smokers, and most
were at least potentially exposed to other lung carcinogens outside NSUK, such as asbestos.
The cohort study findings for lung cancer now appear unremarkable. We have not been able to
explore them further by means of a nested case-control study and therefore cannot make any
fuller assessment of whether any of the known lung carcinogens in use at NSUK might or might
not have contributed to the development of any of the cases. The two industry wide inspection
initiatives undertaken by HSE in 2002 and 2009 do, however, identify the potential for arsenic
exposure in the semiconductor chip manufacturing industry.
5.2.5
Stomach cancer
Though similar to that seen in the original cohort analysis, the finding in relation to female
stomach cancer is of borderline statistical significance. It is based on a small number of cases (5
84
registrations) of which two occurred in the same individual. If the later of these registrations is
excluded, or account is taken of the fact that it is highly unlikely that it represents an
independent incident case, the finding is no longer of even borderline statistical significance.
The fact that only two of the five registrations occurred 10 or more years after the start of
employment at the plant (one of these being the second of two registrations among the same
individual), tends to argue against these findings as evidence of work at NSUK contributing to a
risk of stomach cancer.
Only two stomach cancer cases could be included in the case-only study, neither of which had
accrued any exposure duration for hazards at the plant 10 or more years prior to diagnosis.
Detailed examination of these two cases did not therefore provide any further evidence as to
whether work at the plant increased the risk of stomach cancer.
5.2.6
Brain cancer
Additional follow-up in the cohort analysis did not reveal any further cases of brain cancer, and
the four existing cases do not amount to evidence of a statistically significant excess over the
number expected. There have been no registrations of brain cancer among women so far among
the cohort. Detailed consideration of the 4 male cases did not provide any further clarification
about whether work at NSUK is likely to have resulted in an increased risk of brain cancer.
Information obtained during the course of interviewing relatives of the cases suggested that one
individual had had an additional earlier period of employment at the plant. This would mean
that two (rather than one) of the four cases occurred after 10 years since the start of
employment. Also, whereas none of the four cases had been classified as working in fab areas
for the purposes of the cohort analysis (based on their first job at NSUK) the detailed study of
these four cases suggested that all had done at least some work in fab areas, and two had
accrued employment time in fab areas prior to 10 years before diagnosis. However, there was no
assessed exposure to any of the chemical hazards, other than the one case with some exposure
prior to 5 years before diagnosis, and there was no reported exposure to ionising radiation prior
to 10 years before diagnosis. Only one case was reported as having a maintenance role, although
we cannot be certain that proxy respondents were not aware of cases having done such work.
5.2.7
Colo-rectal cancer
Colo-rectal cancer was not identified as a cancer of concern from the original analysis of this
cohort. We decided to specifically characterise the extent of any excess of cancer registrations
within the general category of cancers of the digestive organs and peritoneum on the basis that
the overall number of male cancer registrations in this category had increased from 3 originally
to 15 in the updated analysis, and of these, 14 had occurred more than 10 years after the start of
employment. Although in itself this is not statistically significantly higher than expected, we
recognised that it could comprise significant excesses for some specific sub-categories that
might plausibly have a common aetiology, such as colo-rectal cancer.
Although the 11 registrations of colo-rectal cancer among men overall is not statistically
significantly higher than expected, the excess based on the 10 cases with time since first
employment restricted to 10 years or more is significant. However, a number of features of the
more detailed analyses tend to reduce the likelihood that this points to work at NSUK being a
cause of some of these cases. Firstly, 2 of the 10 cases were employed for less than 12 months at
the plant; the excess based on the remaining 8 cases is not statistically significant, and there is
no evidence of an increase in the SRRs with increasing duration of employment. In addition,
there was no significant difference in the SRRs for those first employed before or after 1982 –
neither of which was statistically significantly elevated.
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5.3
STRENGTHS AND WEAKNESS OF THE STUDY
The key limitation of the follow-up studies due to their small size has been discussed above.
Another important limitation of the original analysis was the lack of any detailed consideration
of job histories, and the lack of any information about important non-work factors such as
smoking, diet and reproductive history. The more detailed follow-up study was specifically
designed to overcome this limitation in the most efficient way by focussing on the cases of
cancer of most concern and, in the case of breast cancer (and initially lung cancer too) a sample
of controls who had not had the disease. Despite considerable effort to obtain more detailed
information this was not forthcoming, with the exception of breast cancer where there was a
53% per cent response rate. This response rate does limit the numbers available for analysis
however. For 33% of the breast cancer cases, information was provided by proxies rather than
the individual herself.
Increased follow-up in the updated cohort analysis has provided the basis for a fuller
characterisation of the levels of mortality and cancer incidence of these workers compared with
that based on the original study. In particular, it provides stronger evidence in relation to
whether there are any excesses of cancer among the group with time since first employment at
the NSUK plant restricted to 10 years or more – i.e. those most informative with regards
whether work resulted in an increased risk of cancer. In this analysis we were also able to
consider mortality and cancer incidence in relation to duration of work at the plant.
5.3.1
Cohort study
Considerable efforts were made during the original study to ensure the cohort was as complete,
and the information as accurate, as possible. Nevertheless, a subgroup of several hundred
individuals could not be confirmed by NSUK as having worked at the plant. We followed the
same approach here as in the original study and excluded these on the grounds that the low
proportion traced at the NHS Central Register suggested that many of these may have been
foreign nationals.
As discussed in the report of the original cohort study, the best approach for ensuring reference
rates were appropriate for comparison with rates for the cohort was not clear cut, and this raises
a question about the adequacy of the particular approach adopted in this analysis. Our use of the
Carstairs deprivation index to weight national mortality and cancer registration data based on
the available postcode data for NSUK workers does not directly adjust for confounding factors
such as smoking, diet or reproductive history. Nevertheless, as health outcomes correlate
strongly with this index, it is reasonable to consider the adjustment on this basis as controlling at
least partially for these – and other – important socio-economic and lifestyle factors.
We had to make a judgement about whether to base the adjustment on the more recent Scottish
Index of Multiple Deprivation (SIMD) which is available only for national mortality and cancer
registration data from 1997 onwards, or on the Carstairs index, for which data are also available
for earlier periods. Although we have presented our findings based on the latter, overall results
based on the former approach were similar and this suggests our use of the earlier deprivation
index is not a major limitation of this study.
The presence of multiple cancer registrations for individuals introduced a complication in the
analysis since such events will not be independent in all cases. Indeed, some individuals may
have two recorded cancer registrations with the same cancer site and date, as already mentioned
in relation to stomach cancer. In such cases it seems likely that the information reflects a single
cancer event. In other cases multiple cancer events may or may not be independent: individuals
may be more likely to develop cancer at the same or another site in the future once they have
86
had a cancer registration. However, we included all cancer registrations in the analysis, since
excluding any on the grounds that they are unlikely to be independent will introduce a
downward bias in the SRRs due to such events still being included in the reference rates. The
presence of events that are not independent will have resulted in the precision of SRRs being
slightly overestimated in some cases, since 95% confidence intervals were calculated by
assuming they occur independently following a Poisson distribution. Consequently, some
confidence intervals would be wider than reported.
Another issue that had to be taken in to account when making judgements about the statistical
significance of the results is the large number of SMRs and SRRs (with associated 95%
confidence intervals), and hence the large number of significance tests implicit in the analyses
as a whole. The confidence interval for a particular SMR or SRR can be used to judge whether
the number of deaths or cancers actually observed is statistically significantly higher than
expected. At the 5% significance level, 1 in 20 such tests on average would lead to an incorrect
judgement of statistical significance. With a large number of tests the likelihood of some of the
results declared as being statistically significant actually being chance findings is increased. We
chose not to make any adjustment for these multiple comparisons on the grounds that such an
approach can lead to an undue emphasis on the notion of statistical significance in the context of
a study of this size.
Although the updated cohort study included an analysis by duration of employment at the plant,
this did not include any employment after 30 April 1999 for those individuals still in
employment on that date. This might have resulted in a slight tendency to underestimate the
slope in the event of any positive association between the SMR or SRR and increasing duration
of employment. However, given the relatively small proportion of the cohort overall still in
employment on 30 April 1999, and the fact that those affected most will have been employed
more recently – and who are consequently statistically least informative – this effect is likely to
be minimal.
5.3.2
Case-control and case only studies
The important statistical limitation of the breast cancer case-control study because of the small
numbers available for analysis and the possibility of non-response bias has already been
discussed, and these limitations also apply to the case-only studies. It was possible to forward a
request for cooperation with the study via the GP to the vast majority of live cases and control
subjects, and proxies were identified and contacted for all but one of the deceased cases.
Nevertheless, only 21 of the 40 eligible breast cancer cases (or their proxies) at the start of the
recruitment phase agreed to participate, and the response from proxies for the lung cancer study
was < 50%. This demonstrates the difficulty in achieving a good response rate in a case-control
study such as this. The number available for the breast cancer case-control study was judged
sufficient to proceed with the analysis and was broadly consistent with that planned in the
original protocol. Nevertheless, in statistical terms the number was small and limits the potential
of the study to either exclude work at NSUK as having a role in causing the pattern of mortality
and cancer experience seen in the earlier study, or to provide strong evidence for an adverse
effect of one or more work exposures. The low response from proxies for lung cancer cases
resulted in us having to abandon a formal case-control analysis of lung cancer and this was
unfortunate as this was the cancer of most concern based on findings of the original study.
Nevertheless, we respect the decision of those who were asked to help and felt unable to.
Another important source of bias in epidemiological studies is exposure misclassification. We
sought to minimise this by adopting a rigorous exposure assignment strategy which included the
use of structured interviews to elicit job and lifestyle histories, and the assignment of exposures
based on a JEM that was independently derived from a wide ranging historical hygiene
87
assessment. There were a number of limitations associated with the various parts of this process,
as discussed in the following paragraphs. Any exposure misclassification is likely to be nondifferential and therefore, if present, would tend to bias any associations towards the null.
However, overall we do not judge that exposure misclassification is likely to have been a
substantial source of bias such that it would have affected our conclusions.
Seven of the 21 subjects with breast cancer and all of those with the other 3 kinds of cancer
studied were deceased, so there was a need to rely on information from proxy respondents for
these subjects. A number of studies have investigated the reliability of different kinds of
information reported by proxies33,34,35,36,37. Reliability is often dependent on the nature of the
relationship of the proxy to the subject and on the nature of the information being sought.
Though spouses or close family relatives may provide accurate information about lifestyle
factors, they are less likely to provide accurate information about job histories. Thus, we sought
to minimise bias and incompleteness of data by identifying work colleague proxies for job
histories in addition family/relative proxies for lifestyle information. Nevertheless, our
comparison of the reliability of the information provided by additional “false-proxies” for a
sample of subjects where information was also available from the subjects themselves suggested
that assessments of workplace exposure based on proxy information may tend to underestimate
those exposures.
Conversely, any bias resulting from the use of proxy information could operate in the other
direction. For example, a subject who thought that their cancer was caused by their work at
NSUK might tend to discuss their work at NSUK with family members and colleagues which
would result in the proxy knowing more about the subject’s work than the false proxies in our
small evaluation study. This may result in the information that the proxy provides as being more
biased towards what the subject thought was the cause of their illness38.
We thus concluded that the case-control analyses of breast cancer based on subject-only
information were likely to be more reliable than those including the proxy information.
However, those analyses were necessarily based on even smaller numbers (13 cases and 51
controls) and so, although less likely to be subject to bias, were statistically less powerful.
As well as being dependent on the accuracy and completeness of information provided by
subjects or their proxies, the individual exposure assignment was also reliant on the accuracy of
the JEM developed from the HHA. It was judged by an experienced industrial hygienist that
there were insufficient empirical exposure measurements for chemicals used at NSUK to allow
assessments to be made of the likely intensities of historical exposures to those chemicals. As a
result, it was not possible to assess risk in relation to quantitative exposure. The JEM produced
was limited to binary categories (potential for exposure or not), and combining those with work
history data allowed the construction of variables representing durations of exposure.
Another error that could have affected our results is if we had not adequately controlled for
confounding factors. Many lifestyle factors have been identified as potential confounders in
studies of cancer aetiology and in the case of breast cancer many aspects of reproductive history
are relevant. The approach we adopted to collecting data on such factors was designed to strike
a balance between questionnaire length and complexity, and the need for sufficient information
to address the most important potential confounders for breast (and lung) cancer in the context
of a study of this size and scope. Our results for breast cancer in relation to the potential NSUK
hazards considered were not sensitive to whether or not we made adjustment for these main
lifestyle factors. It is therefore unlikely that our results would be changed had we been able to
adjust for more subtle effects of the full range of potential lifestyle factors. The fact that all of
the lung cancers we studied were smokers also implies that further more rigorous assessment of
other potential confounders would not change our conclusions on that cause.
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5.4
INTERPRETATION OF FINDINGS IN THE CONTEXT OF OTHER STUDIES
To date, there have been a limited number of epidemiological studies of cancer risk among
semiconductor workers. This cohort of workers at NSUK, Greenock, represents one of two in
the UK where levels mortality and cancer incidence have been investigated, the other being a
cohort of 1807 workers at a West Midlands semiconductor factory39. In addition to these
studies, mortality has been investigated among a large cohort of workers employed at three IBM
manufacturing facilities in the US5 and, more recently, cancer incidence has also been
investigated among workers employed at two of these sites6. Emerging findings from
investigations of cancer risks in a large cohort of semiconductor workers in Korea40 and further
cohort in Taiwan41 have also been published, though in both cases the length of follow-up was
limited.
The extent to which the results of these studies (including ours) can be used collectively to
provide greater insight into whether work in the semiconductor industry can be associated with
an increased risk of cancer depends on the extent to which exposures and work practices were
similar at the various sites studied. Some caution is required when comparing the results of
these studies. For example, the authors of the most recent analysis of the West Midlands cohort
noted that a lack of agreement in the results with those of the original NSUK study might
simply be a reflection of the fact that exposures could have been very different at each site. It is
clear that there were differences in the operations carried out at the sites within the IBM study
and these could have led to different exposures. In particular, one of the sites (San Jose)
manufactured disk drives, tape drives network servers and microdrives which involved different
process and chemicals than the other two sites. Nevertheless a number of toxic substances have
been in widespread use across the industry for many years, meaning that comparisons are not
entirely without justification.
The results of the HHA14 carried out during the course of our study may help in the
interpretation of future more informative analyses of the above cohorts, and the yet to be
published US Semiconductor Industry Association study, by providing an insight into
similarities and differences in work processes and potential exposures at the NSUK Greenock
plant and other sites.
Of the four cancer sites that have been the focus of concern at the NSUK plant, only in the case
of brain cancer has there been any particular suggestion of an excess in other studies. In the
IBM studies, work in process equipment maintenance at the East Fishkill facility was associated
with increased mortality and incidence of central nervous system cancers and for mortality there
was a positive trend with duration of employment. The authors concluded that further work to
assess any relation to work place exposures would be warranted. In contrast to these findings,
there was no suggestion of excess risks of brain cancer among the West Midlands
semiconductor cohort, though this was a much smaller study. There was no evidence of an
association with maintenance work in our study with only one case reported as having a
maintenance role.
As in our original and updated cohort analyses, the IBM studies found differences in lung
cancer mortality between males and females, with SMRs for women tending to be noticeably
higher overall, and in most sub-groups, than those for men. However, those differences
persisted when separate analyses were conducted for groups categorised as unexposed as well as
exposed, and the differences were also present at the San Jose facility where the processes and
chemicals used were described as different from those at the other two facilities studied. Both
these findings tend to argue against the differences between males and females being suggestive
of a workplace cause more relevant to women. Furthermore, lung cancer incidence tended to be
lower than expected, with similar levels for both men and women at both the San Jose and East
89
Fishkill plants. Although an association between increased lung cancer incidence and masking
work was seen among women at the IBM East Fishkill facility, this was confined mainly to
short term workers and there was no trend with duration of employment that might be indicative
of a workplace cause. Increased lung cancer mortality associated with masking work was seen
at the IBM Burlington site, but this was based on small numbers and again there was no trend
with duration of employment. The evidence from the studies at IBM are consistent with our
findings in that they do not provide any convincing evidence of a workplace risk of lung cancer.
There was no overall excess of breast cancer mortality or incidence in the IBM or West
Midlands cohorts. Although there was an association between increased breast cancer mortality
and masking work at the IBM Burlington site, the results were based on small numbers and
occurred among those with shorter employment duration and time since hire. Again, although
breast cancer was listed as one of those cancer sites for which associations with an increased
risk were seen for some of the employment subgroups within the IBM cancer incidence study,
the authors concluded that these findings are explicable in terms of the higher socio-economic
status of these workers. Overall these findings do not provide any convincing evidence of an
occupational risk of breast cancer.
Findings from other semiconductor cohort studies in respect of colo-rectal cancer do not provide
any further insights into our results. An excess of rectal cancer registrations was seen within the
West Midlands cohort study, but this was based on a small number of cases and, on the basis of
more detailed analyses, the authors expressed doubt about this being occupationally related.
Colon cancer is mentioned as one of those for which associations with an increased risk were
seen for some of the employment subgroups within the IBM cancer incidence study. However,
as with breast cancer, the authors conclude that these findings are explicable in terms of the
higher socio-economic status of these workers. An increased risk of colo-rectal cancer mortality
was not a feature of the IBM study. A Canadian population based case-control study
investigated associations between various cancers and exposure to solvents, but did not find
persuasive evidence that increased risks could be directly related to exposure42. There was some
suggestion of possible excess risks of both colon and rectal cancer in relation to exposure to
xylene. However, we are not aware of any other studies that have replicated these tentative
findings.
Study of the West Midlands semiconductor workers was originally motivated by the
investigation of an apparent cluster of malignant melanoma at the factory, and the most recent
update of that cohort did reveal an overall excess of melanoma cancer registrations among men
and women combined, although the authors express some doubt about whether this is likely to
be occupationally related. Increased incidences of melanoma were seen for some of the
subgroups at one of the sites in the IBM study – but these were either confined to those with
short durations of employment or based on small numbers of cases. We found no suggestion of
an excess of melanoma within the NSUK cohort.
We included ovarian cancer as one of the cancer sites for study in our updated cohort analysis
because of the reported excess due to this cancer in the IBM mortality study which was most
strongly associated with work in clean rooms. There was no excess of ovarian cancer in the
more recent IBM cancer incidence study, and mortality and incidence of ovarian cancer were
consistent with expectation both in the West Midlands study and our study of NSUK workers.
90
6 CONCLUSIONS Our new research does not support the earlier concerns about a link between working at NSUK
and developing cancer, especially when taking account of new information about cancer at two
IBM semiconductor factories in America.
The evidence from this most recent study does not prompt us to recommend any further
epidemiological research in the way the evidence from previous study did. In any case there is
nothing more that could be done within the NSUK setting at this stage.
The Historical Hygiene Assessment that was undertaken as part of this study should provide a
valuable resource for the local interpretation of any further evidence that may emerge about
cancer in the semiconductor industry as a consequence of studies now underway or undertaken
in the future.
91
7
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94
APPENDIX 1 – ADDITIONAL RESULTS TABLES AND CHARTS
The results in the following tables are for the entire case-control dataset. The description of
duration of exposure to each hazard, with no adjustment for latency (Table A1.1) as well as 5
year latency adjustment (Table A1.2), are shown. Subsequent tables illustrate the results of the
conditional logistic regression analyses for both ever-never exposed and duration exposed with
no adjustment for latency (Tables A1.3 and A1.5) as well as adjustment for 5-year latency
(Tables A1.4 and A1.6).
Table A1.1 Number of people ‘ever’ exposed to each hazard and the mean, median
and standard deviation duration exposed for cases and controls for no year latency
period
Case (n = 20)
Control (n = 83)
Ever Med Mean Max
SD Ever Med Mean Max SD
Acid
16 5.16
7.23 21.76 6.68 67 3.06
4.58 20.00 4.98
Solvent
10 0.16
1.96 11.00 2.97 52 0.57
1.50 11.81 2.16
Gases
12 0.51
2.86 17.67 4.32 47 0.21
1.19 9.36 1.96
Antimony
trioxide Arsenic and its compounds
Carbon fibre
Ceramic
Chromium
trioxide and
chromic acid
Trichloroethylene
Sulphuric acid
mist
10
0.00
1.92
8.27
2.92
38
0.00
0.93
15.00 2.11
10
0.00
2.33
16.67
4.13
36
0.00
0.81
8.06 1.58
3
3
0.00
0.00
0.38
0.23
3.36
2.10
0.98
0.60
19
10
0.00
0.00
0.19
0.09
2.88 0.50
1.67 0.31
6
0.00
1.07
17.37
3.77
28
0.00
0.27
2.50 0.50
1
0.00
0.13
2.83
0.62
5
0.00
0.09
3.00 0.43
15
4.00
5.92
20.37
6.34
65
2.17
3.33
18.33 4.02
Ionising Radiation
Non-ionising RF
Non-ionising UV
6
7
17
0.00
0.00
8.30
0.86
1.96
7.95
6.40
17.37
21.76
1.82
4.10
6.31
28
40
76
0.00
0.00
4.74
0.63
0.84
5.52
7.00 1.28
9.33 1.45
20.00 4.65
Building
Fab
15
16
6.59
9.13
7.49
8.58
23.16
23.16
7.28
7.12
64
70
4.00
5.00
6.71
7.23
23.75 6.93
23.75 6.80
Nightshift
Rotational
Circadian
13
8
13
3.19
0.00
3.19
3.94
2.17
3.94
14.66
14.66
14.66
4.37
3.79
4.37
49
26
49
1.00
0.00
1.00
4.04
1.67
4.04
19.00 5.28
14.37 3.29
19.00 5.28
Non-NSUK
Nightshift
Rotational
Circadian
Other semi
0
1
1
1
0.00
0.00
0.00
0.00
0.00
0.02
0.02
0.02
0.00
0.50
0.50
0.34
0.00
0.11
0.11
0.07
18
23
27
5
0.00
0.00
0.00
0.00
1.28
1.59
2.26
0.28
18.72
25.18
25.18
10.00
32.58
11.21
13.75
31.32
11.35
13.33
46.61
23.16
24.75
9.15
6.21
5.84
33.38
8.81
12.23
31.20
9.24
13.64
55.53 9.42
28.00 6.64
37.93 8.73
Employment Duration
Total
NSUK
Non-NSUK
95
3.46
3.97
4.77
1.53
Table A1.2 Number of people ‘ever’ exposed to each hazard and the mean, median
and standard deviation duration exposed for cases and controls for a 5 year latency
period
Case (n = 20)
Control (n = 83)
Ever Med Mean Max SD Ever Med Mean Max
SD
Acid
15
3.01
5.37 16.76 5.78
61
2.15
3.61 17.41 4.13
0.11
1.49 11.00 2.64
1.23 7.81 1.23
Solvent
11
46 0..34
0.51
2.06 12.67 3.21
0.95 8.29 1.66
0.00
Gases
12
40
Antimony
trioxide
Arsenic and its
compounds
Carbon fibre
Ceramic
Chromium
trioxide and
chromic acid
Trichloroethylene
Sulphuric acid
mist
10
0.00
1.36
7.55 2.29
35
0.00
0.78 15.00
1.95
10
0.00
1.65
11.67 3.00
33
0.00
0.66
7.77
1.33
3
3
0.00
0.00
0.28
0.16
2.42 0.73
1.27 0.41
14
9
0.00
0.00
0.13
0.07
2.88
1.00
0.41
0.22
6
0.00
0.77
12.37 2.69
25
0.00
0.23
2.50
0.46
1
0.00
0.11
2.27 0.50
5
0.00
0.09
3.00
0.42
14
2.06
4.45
16.00 5.48
59
1.40
2.66 16.61
3.46
Ionising radiation
Non-ionising RF
Non-ionising UV
6
7
17
0.00
0.00
3.88
0.72
1.55
5.71
6.40 1.73
12.37 3.09
16.76 5.20
25
34
68
0.00
0.00
3.44
0.49 6.22
0.65 8.29
4.34 17.41
1.07
1.23
4.14
Building
Fab
15
16
3.00
4.65
5.30
6.29
18.16 5.96
18.16 5.90
58
62
2.75
3.50
5.25 18.75
5.63 18.73
5.87
5.80
Nightshift
Rotational
Circadian
13
8
13
0.90
0.00
0.90
2.63
1.24
2.63
9.66 3.21
9.66 2.42
9.66 3.21
42
18
42
0.91
0.00
0.91
3.05 17.50
1.03 13.50
3.05 17.50
4.37
2.53
4.37
0
1
1
1
0.00
0.00
0.00
0.00
0.00
0.02
0.02
0.02
0.00
0.50
0.50
0.34
13
18
21
4
0.00
0.00
0.00
0.00
0.84
1.19
1.55
0.26
12.00
21.18
21.18
10.00
2.39
3.23
3.65
1.50
28.53
7.39
11.95
27.00
8.37
12.45
26.74 45.53
7.13 23.92
11.91 32.93
9.37
5.85
7.69
Non-NSUK
Nightshift
Rotational
Circadian
Other semi
Employment Duration
Total
NSUK
Non-NSUK
0.00
0.11
0.11
0.07
41.61 9.25
18.16 5.65
24.75 5.90
96
29.00
6.30
10.08
Table A1.3 Results of conditional logistic regressions for ever/never exposed factors,
for no latency period. The table shows the odds ratio and 95% confidence interval
Ever Exposed Odds Ratio
95% Confidence Interval Acid
0.91
0.24
3.41
Solvent
0.58
0.21
1.56
Gases
1.10
0.39
3.07
Antimony Trioxide
Arsenic and its compounds
Carbon Fibre
Ceramic
Chromium
Trichloroethylene
Sulphuric Acid Mist
1.13
1.25
0.62
1.20
0.86
0.83
0.78
0.43
0.46
0.17
0.29
0.31
0.10
0.24
3.01
3.38
2.24
5.07
2.39
7.16
2.54
Ionising Radiation
Non-Ionising Radiation RF
Non-Ionising Radiation UV
0.84
0.60
0.42
0.29
0.23
0.08
2.43
1.57
2.25
Building
Fab
0.86
0.72
0.28
0.20
2.69
2.60
Nightshift
Rotational
Circadian
1.31
1.97
1.31
0.45
0.55
0.45
3.79
7.12
3.79
0.01
0.01
0.09
1.05
0.82
7.79
Non-NSUK
Nightshift*
Rotational
0.12
Circadian
0.10
Other Semi
0.85
*Odds Ratios were unable to be calculated for these hazards
97
Table A1.4 Results of conditional logistic regressions for ever/never exposed factors,
for a 5 year latency period. The table shows the odds ratio and 95% confidence
interval.
Ever Exposed
Odds Ratio
95% Confidence Interval
Acid
1.07
0.31
3.67
Solvent
0.78
0.29
2.12
Gases
1.61
0.57
4.54
Antimony trioxide
Arsenic and its compounds
Carbon fibre
Ceramic
Chromium
Trichloroethylene
Sulphuric acid mist
1.31
1.45
0.87
1.38
0.99
0.83
0.91
0.50
0.54
0.23
0.31
0.35
0.10
0.30
3.46
3.88
3.33
6.11
2.77
7.16
2.78
Ionising radiation
Non-Ionising radiation RF
Non-Ionising radiation UV
0.99
0.76
1.24
0.34
0.28
0.29
2.88
2.05
5.39
Building
Fab
1.25
1.42
0.41
0.36
3.88
5.56
Nightshift
Rotational
Circadian
1.99
1.95
1.99
0.67
0.54
0.67
5.96
7.01
5.96
0.02
0.02
0.11
1.36
1.12
10.87
Non-NSUK
Nightshift*
Rotational
0.15
Circadian
0.13
Other Semi
1.10
*Odds Ratios were unable to be calculated for these hazards
98
Table A1.5 Results of conditional logistic regressions for duration exposed to each of
the hazards, with no latency period, as well as for the log of the duration exposed.
Duration Exposed
Duration Exposed Logged
Odds
95% Confidence
Odds
95% Confidence
Ratio
Interval
Ratio
Interval
Acid
1.11
1.00
1.23
1.13
0.87
1.48
Solvent
1.08
0.89
1.31
0.96
0.74
1.24
Gases
1.30
1.05
1.60
1.18
0.90
1.55
Antimony trioxide
Arsenic and its compounds
Carbon fibre
Ceramic
Chromium
Trichloroethylene
Sulphuric acid mist
1.17
1.29
1.46
2.20
1.29
1.21
1.14
0.98
1.04
0.78
0.70
0.79
0.50
1.02
1.40
1.59
2.74
6.91
2.10
2.93
1.26
1.14
1.19
1.02
1.23
1.06
1.02
1.13
0.88
0.91
0.69
0.75
0.76
0.57
0.87
1.47
1.54
1.51
2.01
1.49
1.83
1.48
Ionising Radiation
Non-ionising radiation RF
Non-ionising radiation UV
1.11
1.30
1.11
0.82
0.97
1.00
1.51
1.75
1.23
0.97
0.99
1.07
0.73
0.76
0.78
1.31
1.28
1.47
Building
Fab
1.02
1.03
0.95
0.95
1.10
1.11
1.03
1.04
0.82
0.81
1.28
1.34
Nightshift
Rotational
Circadian
0.99
1.05
0.99
0.90
0.92
0.90
1.10
1.20
1.10
1.06
1.10
1.06
0.85
0.88
0.85
1.31
1.37
1.31
Non-NSUK
Nightshift*
Rotational
Circadian
Other Semi
0.22
0.22
0.57
0.01
0.01
0.05
3.79
3.57
7.13
0.52
0.50
0.80
0.25
0.25
0.36
1.05
1.00
1.77
Employment
Total
1.01
0.92
1.10
NSUK
1.06
0.97
1.15
Non-NSUK
1.00
0.93
1.06
*Odds Ratios were unable to be calculated for these hazards
1.47
1.60
0.85
0.14
0.87
0.52
15.73
2.97
1.40
99
Table A1.6 Results of conditional logistic regressions for duration exposed to each of
the hazards, with a 5 year latency period, as well as for the log of the duration exposed
Duration Exposed
Duration Exposed Logged
Odds
95% Confidence
Odds
95% Confidence
Ratio
Interval
Ratio
Interval
Acid
1.10
0.98
1.25
1.10
0.84
1.45
Solvent
1.07
0.83
1.36
0.96
0.73
1.26
1.30
Gases
1.02
1.66
1.22
0.92
1.61
Antimony trioxide
Arsenic and its compounds
Carbon fibre
Ceramic
Chromium
Trichloroethylene
Sulphuric acid mist
1.13
1.30
1.61
2.92
1.33
1.12
1.13
0.93
1.01
0.72
0.60
0.80
0.41
1.00
1.39
1.67
3.58
14.26
2.20
3.05
1.27
1.15
1.19
1.12
1.26
1.08
1.01
1.12
0.88
0.90
0.73
0.74
0.76
0.55
0.85
1.51
1.58
1.71
2.17
1.55
1.86
1.46
Ionising Radiation
Non-ionising radiation RF
Non-ionising radiation UV
1.15
1.43
1.09
0.82
0.99
0.96
1.61
2.07
1.24
0.99
1.04
1.13
0.72
0.78
0.82
1.35
1.39
1.55
Building
Fab
1.01
1.02
0.92
0.93
1.10
1.12
1.06
1.10
0.84
0.84
1.33
1.44
Nightshift
Rotational
Circadian
0.97
1.04
0.97
0.85
0.87
0.85
1.10
1.24
1.10
1.07
1.15
1.07
0.85
0.90
0.85
1.35
1.47
1.35
Non-NSUK
Nightshift*
Rotational
Circadian
Other Semi
0.25
0.23
0.62
0.02
0.01
0.05
3.87
3.87
7.16
0.54
0.53
0.84
0.27
0.26
0.39
1.10
1.06
1.83
1.66
1.60
0.93
1.66
1.60
0.93
1.66
1.60
0.93
Employment
Total
1.02
0.91
1.13
NSUK
1.05
0.95
1.15
1.02
Non-NSUK
0.94
1.09
*Odds Ratios were unable to be calculated for these hazards
100
The results in the following tables are for the dataset with proxies removed. The description of
duration of exposure to each hazard, with no adjustment for latency (Table A1.7) as well as 5
year latency adjustment (Table A1.8), are shown. Subsequent tables illustrate the results of the
conditional logistic regression analyses for both ever-never exposed and duration exposed with
no adjustment for latency (Tables A1.9 and A1.11) as well as adjustment for 5-year latency
(Tables A1.10 and A1.12).
Table A1.7 Number of people ‘ever’ exposed to each hazard and the mean, median
and standard deviation duration exposed for cases and controls for no year latency
period. This information is shown for the dataset with proxies removed.
Case (n = 13)
Control (n = 51)
Ever Med Mean Max SD Ever Med Mean
Max
SD
Acid
10 4.94
7.53 21.76 7.55 42 3.21
4.75
18.65 4.77
Solvent
5 0.00
1.99 11.00 3.49 37 0.75
1.82
11.81 2.40
Gases
9 2.10
3.41 17.67 4.94 30 0.42
1.05
9.33 1.63
Antimony
trioxide
Arsenic and its
comounds
Carbon fibre
Ceramic
Chromium
trioxide and
chromic acid
Trichloroethylene
Sulphuric acid
mist
8
0.51
2.33
8.18
2.97
23
0.00
0.62
4.60
1.11
8
0.51
2.99
16.67
4.72
23
0.00
0.60
4.67
1.02
1
2
0.00
0.00
0.22
0.24
2.83
2.10
0.79
0.62
13
7
0.00
0.00
0.25
0.11
2.88
1.67
0.59
0.33
3
0.00
1.48
17.37
4.79
16
0.00
0.25
2.33
0.47
1
0.00
0.22
2.83
0.79
4
0.00
0.12
3.00
0.53
10
4.94
6.83
20.37
7.20
40
2.21
3.22
16.34
3.58
Ionising radiation
Non-ionising RF
Non-ionising UV
5
5
11
0.00
0.00
4.94
1.25
2.56
7.42
6.40
17.37
21.76
2.21
5.00
6.85
19
28
0.00
0.23
5.56
0.63
0.99
5.60
7.00
9.33
14.87
1.29
1.58
4.38
Building
Fab
10
9
4.50
3.09
7.33
7.25
23.16
23.16
7.72
8.00
43
45
5.30
6.85
7.39
7.74
23.75
23.75
6.86
6.82
Nightshift
Rotational
Circadian
9
4
9
3.09
0.00
3.09
3.83
1.77
3.83
14.66
14.66
14.66
4.49
4.14
4.49
28
15
28
0.96
0.00
0.96
3.69
1.33
3.69
19.00
13.50
19.00
5.22
2.76
5.22
Non-NSUK
Nightshift
Rotational
Circadian
Other semi
0
1
1
0
0.00
0.00
0.00
0.00
0.00
0.04
0.04
0.00
0.00
0.50
0.50
0.00
0.00
0.14
0.14
0.00
10
12
15
3
0.00
0.00
0.00
0.00
1.28
1.43
2.12
0.26
18.72
14.00
18.72
10.00
3.77
3.48
4.52
1.43
31.75
12.00
12.36
30.45
11.51
12.01
46.61
23.16
23.81
9.03
7.08
5.59
31.07
8.81
11.67
28.56
8.94
13.25
Employment Duration
Total
NSUK
Non-NSUK
101
55.53 10.74
23.75 6.34
37.93 9.54
Table A1.8 Number of people ‘ever’ exposed to each hazard and the mean, median
and standard deviation duration exposed for cases and controls for a 5 year latency
period. This information is shown for the dataset with proxies removed
Case (n = 13)
Control (n = 51)
Ever Med Mean Max SD Ever Med Mean Max SD
Acid
9
2.83
6.10 16.76 6.66 39 2.18
3.80 16.58 4.11
Solvent
4
0.00
1.64 11.00 3.18 34 0.66
1.50
7.81 1.92
Gases
9
0.80
2.69 12.67 3.83 27 0.21
0.85
8.29 1.47
Antimony trioxide
Arsenic and its
compounds
Carbon fibre
Ceramic
Chromium trioxide
and chromic acid
Trichloroethylene
Sulphuric acid mist
8
0.51
1.86
7.55 2.69
21
0.00
0.52
4.60
1.06
8
0.51
2.32
11.67 3.59
21
0.00
0.50
4.14
0.94
1
2
0.00
0.00
0.17
0.17
2.27 0.63
1.27 0.43
11
6
0.00
0.00
0.18
0.08
2.88
1.00
0.49
0.23
3
0.00
1.09
12.37 3.41
15
0.00
0.22
2.07
0.43
1
9
0.00
2.06
0.17
5.57
2.27 0.63
16.00 6.42
4
37
0.00
1.43
0.12
2.62
3.00
14.53
0.53
3.27
Ionising radiation
Non-ionising RF
Non-ionising UV
5
5
11
0.00
0.00
2.83
1.09
2.08
5.90
6.40 2.12
12.37 3.76
16.76 5.83
17
25
44
0.00
0.00
2.90
0.54
0.81
4.42
6.22
8.29
14.55
1.18
1.41
4.08
Building
Fab
10
9
2.83
2.83
5.68
5.99
18.16 6.75
18.16 6.94
40
42
3.13
3.79
5.80
6.14
18.75
18.73
6.00
6.00
Nightshift
Rotational
Circadian
9
4
9
1.00
0.00
1.00
2.82
1.16
2.82
9.66 3.51
9.66 2.80
9.66 3.51
24
11
24
0.00
0.00
0.00
2.91
0.78
2.91
17.50
13.50
17.50
4.55
2.21
4.55
Non-NSUK
Nightshift
Rotational
Circadian
Other semi
0
1
1
0
0.00
0.00
0.00
0.00
0.00
0.04
0.04
0.00
0.00
0.50
0.50
0.00
9
11
14
3
0.00
0.00
0.00
0.00
0.92
1.08
1.54
0.23
12.00
12.00
12.00
10.00
2.62
2.67
3.29
1.40
26.77
10.00
10.00
26.07
9.20
10.73
41.61 9.11
18.16 6.47
23.50 5.29
27.07
5.61
9.00
23.98
7.06
11.44
45.53 14.36
18.75 5.77
32.93 8.34
Employment Duration
Total
NSUK
Non-NSUK
102
0.00
0.14
0.14
0.00
Table A1.9 Results of conditional logistic regressions for ever/never exposed factors,
for no latency period. This information is shown for the dataset with proxies removed
Ever Exposed Odds Ratio
95% Confidence Interval Acid
0.70
0.15
3.33
Solvent
0.23
0.06
0.85
Gases
1.54
0.41
5.79
Antimony trioxide
Arsenic and its compounds
Carbon fibre
Ceramic
Chromium
Trichloroethylene
Sulphuric acid mist
1.82
1.82
0.28
1.09
0.66
1.04
0.90
0.54
0.54
0.03
0.19
0.17
0.12
0.21
6.10
6.10
2.22
6.31
2.61
9.37
3.86
Ionising radiation
Non-ionising radiation RF
Non-ionising radiation UV
1.06
0.55
0.41
0.32
0.17
0.05
3.55
1.76
3.07
Building
Fab
0.71
0.26
0.16
0.04
3.20
1.52
Nightshift
Rotational
Circadian
2.05
1.03
2.05
0.54
0.28
0.54
7.72
3.85
7.72
Non-NSUK
Nightshift*
Rotational
0.23
0.02
Circadian
0.18
0.02
Other Semi*
*Odds Ratios were unable to be calculated for these hazards
2.30
1.64
103
Table A1.10 Results of conditional logistic regressions for ever/never exposed factors,
for a 5 latency period. The table shows the odds ratio and 95% confidence interval.
This information is shown for the dataset with proxies removed
Ever Exposed
Odds Ratio
95% Confidence Interval
Acid
0.62
0.13
2.91
Solvent
0.29
0.08
1.09
Gases
2.04
0.53
7.77
Antimony trioxide
Arsenic and its compounds
Carbon fibre
Ceramic
Chromium
Trichloroethylene
Sulphuric acid mist
2.13
2.13
0.33
1.32
0.72
1.04
0.82
0.63
0.63
0.04
0.21
0.18
0.12
0.20
7.19
7.19
2.71
8.43
2.87
9.37
3.35
Ionising radiation
Non-ionising radiation RF
Non-ionising radiation UV*
1.24
0.65
0.37
0.19
4.15
2.18
Building
Fab
1.03
0.36
0.23
0.06
4.64
2.23
Nightshift
Rotational
Circadian
3.22
1.61
3.22
0.77
0.39
0.77
13.50
6.71
13.50
0.02
0.02
2.49
1.76
Non-NSUK
Nightshift*
Rotational
0.24
Circadian
0.19
Other Semi*
*Odds Ratios were unable to be calculated for these hazards
104
Table A1.11 Results of conditional logistic regressions for duration exposed to each of
the hazards, with no latency period, as well as for the log of the duration exposed. This
information is shown for the dataset with proxies removed
Duration Exposed
Duration Exposed Logged
Odds
95% Confidence
Odds
95% Confidence
Ratio
Interval
Ratio
Interval
Acid
1.15
0.98
1.36
1.05
0.76
1.45
Solvent
1.02
0.87
1.20
0.79
0.57
1.11
Gases
1.49
1.07
2.09
1.25
0.88
1.77
Antimony trioxide
Arsenic and its compounds
Carbon fibre
Ceramic
Chromium
Trichloroethylene
Sulphuric acid mist
1.47
1.63
0.90
2.01
1.26
1.26
1.19
1.07
1.10
0.33
0.47
0.79
0.52
1.02
2.01
2.42
2.47
8.55
1.99
3.05
1.40
1.29
1.34
0.75
1.17
0.99
1.08
1.14
0.93
0.95
0.41
0.64
0.64
0.60
0.81
1.78
1.88
1.40
2.14
1.53
1.95
1.60
Ionising radiation
Non-ionising radiation RF
Non-ionising radiation UV
1.20
1.29
1.08
0.87
0.92
0.94
1.66
1.80
1.24
1.04
0.96
0.98
0.75
0.70
0.67
1.44
1.32
1.43
Building
Fab
0.99
0.98
0.90
0.89
1.10
1.08
0.96
0.83
0.72
0.60
1.28
1.14
Nightshift
Rotational
Circadian
1.01
1.04
1.01
0.88
0.85
0.88
1.14
1.26
1.14
1.13
1.01
1.13
0.86
0.74
0.86
1.47
1.37
1.47
Non-NSUK
Nightshift*
Rotational
Circadian
Other Semi*
0.35
0.31
0.03
0.02
4.34
4.05
0.60
0.57
0.30
0.29
1.21
1.14
Employment
Total
1.06
0.92
1.21
NSUK
1.08
0.96
1.21
Non-NSUK
0.98
0.91
1.06
*Odds Ratios were unable to be calculated for these hazards
15.80
1.53
1.19
0.25
0.74
0.53
1007.47
3.18
2.67
105
Table A1.12 Results of conditional logistic regressions for duration exposed to each of
the hazards, with a 5 latency period, as well as for the log of the duration exposed. This
information is shown for the dataset with proxies removed
Duration Exposed
Duration Exposed Logged
Odds
95% Confidence
Odds
95% Confidence
Ratio
Interval
Ratio
Interval
Acid
1.16
0.97
1.38
1.02
0.72
1.44
Solvent
1.03
0.78
1.36
0.80
0.56
1.13
Gases
1.51
1.06
2.15
1.31
0.90
1.90
Antimony trioxide
Arsenic and its compounds
Carbon fibre
Ceramic
Chromium
Trichloroethylene
Sulphuric acid mist
1.45
1.60
0.97
2.77
1.35
1.17
1.19
1.03
1.08
0.30
0.40
0.76
0.44
1.01
2.04
2.39
3.16
19.19
2.40
3.14
1.40
1.34
1.38
0.80
1.22
1.02
1.07
1.12
0.95
0.96
0.41
0.63
0.65
0.58
0.78
1.90
1.98
1.56
2.35
1.60
1.97
1.60
Ionising radiation
Non-ionising radiation RF
Non-ionising radiation UV
1.21
1.39
1.11
0.85
0.94
0.93
1.71
2.06
1.32
1.05
1.00
1.05
0.75
0.71
0.70
1.48
1.40
1.59
Building
Fab
0.99
0.99
0.88
0.88
1.11
1.11
0.99
0.87
0.73
0.62
1.35
1.23
Nightshift
Rotational
Circadian
1.00
1.05
1.00
0.86
0.83
0.86
1.16
1.34
1.16
1.18
1.09
1.18
0.87
0.77
0.87
1.59
1.54
1.59
Non-NSUK
Nightshift*
Rotational
Circadian
Other Semi*
0.33
0.28
0.02
0.02
4.34
4.12
0.60
0.57
0.29
0.28
1.23
1.15
23.81
1.80
1.30
0.44
0.83
0.57
1297.77
3.90
2.96
Employment
Total
1.11
0.93
1.33
NSUK
1.10
0.95
1.27
Non-NSUK
0.98
0.90
1.07
*Odds Ratios were unable to be calculated for these hazards
106
Figure A1.1 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Acids (left); Solvents (centre); Gases (right). Durations are adjusted for a 10 year latency
period. The solid upward pointing triangles (▲) are influential cases, while the solid downward pointing triangles (▼) are influential cases
where one of their controls is also influential. These plots are for the dataset excluding proxy case-control sets.
Solvents
00
=1
x ca
0
=1
x ca
0.01
0.1
.1
Ratio of case exposure to controls' geometric mean
=1
x ca
107
0.1
=0
x ca
Geometric mean exposure of
case-control set (years)
1
1
10
10
.0
.1
1
100
=0
x ca
1
0.1
=0
x ca
0.01
.0
Geometric mean exposure of
case-control set (years)
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
1
0
0
1
.0
0.1
=0
x ca
0.01
10
=1
x ca
=1
x ca
0.1
100
00
00
1
Gases
=1
x ca
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
=0
x ca
Ratio of case exposure to controls' geometric mean
Acids
1
10
Geometric mean exposure of
case-control set (years)
Figure A1.2 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Arsenic and its compounds (left); Antimony trioxide (centre); Carbon tetrachloride (right).
Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲) are influential cases, while the solid
downward pointing triangles (▼) are influential cases where one of their controls is also influential. These plots are for the dataset
excluding proxy case-control sets.
=1
x ca
0
=1
x ca
Ratio of case exposure to controls' geometric mean
00
0.01
0.1
.1
Ratio of case exposure to controls' geometric mean
=1
x ca
108
0.1
=0
x ca
Geometric mean exposure of
case-control set (years)
1
1
10
10
.0
.1
1
100
=0
x ca
1
0.1
=0
x ca
0.01
.0
Geometric mean exposure of
case-control set (years)
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
0
0
=0
x ca
1
.0
0.1
1
=1
x ca
=1
x ca
0.1
10
00
00
1
100
=1
x ca
=1
x ca
10
=0
x ca
Ratio of case exposure to controls' geometric mean
100
0.01
Carbon Tetrachloride
Antimony Trioxide
Arsenic
1
10
Geometric mean exposure of
case-control set (years)
Figure A1.3 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Ceramic fibre (left); Chromium Trioxide and Chromic Acid (centre-left); Sulphuric acid mist
(centre-right); Trichloroethylene (right). Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲) are
influential cases, while the solid downward pointing triangles (▼) are influential cases where one of their controls is also influential. These
plots are for the dataset excluding proxy case-control sets.
Ratio of case exposure to controls' geometric mean
Ratio of case exposure to controls' geometric mean
1
109
0.1
.
=0
x ca
10
0.01
1
1
Geometric mean exposure of
case-control set (years)
0.1
.0
=0
x ca
1
0.1
Geometric mean exposure of
case-control set (years)
1
=1
x ca
=1
x ca
0.01
10
0
=1
x ca
0
=1
x ca
0.1
100
00
=1
x ca
1
.
=0
x ca
10
10
1
1
100
.0
=0
x ca
1
0.1
.
=0
x ca
0.01
1
10
.0
=0
x ca
1
1
0.1
=1
x ca
=1
x ca
.
=0
x ca
1
0.1
Geometric mean exposure of
case-control set (years)
1
0
=1
x ca
0
=1
x ca
0.1
10
Trichloroethylene
00
=1
x ca
1
100
00
=1
x ca
00
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
0.01
Sulphuric Acid Mist
Chromium Trioxide and Chromic Acid
.0
=0
x ca
Ratio of case exposure to controls' geometric mean
Ceramic Fibre
1
10
Geometric mean exposure of
case-control set (years)
Figure A1.4 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Ionising radiation (left); Non-ionising radiation Radio Frequency (centre); Non-ionising
radiation Ultra-Violet (right). Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲) are influential
cases, while the solid downward pointing triangles (▼) are influential cases where one of their controls is also influential. These plots are
for the dataset excluding proxy case-control sets.
Non-Ionising RF Radiation
00
=1
x ca
0
=1
x ca
0.01
0.1
.1
Ratio of case exposure to controls' geometric mean
=1
x ca
110
0.1
=0
x ca
10
1
1
.1
1
10
.0
1
.0
0.1
Geometric mean exposure of
case-control set (years)
100
=0
x ca
0.01
=0
x ca
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
Geometric mean exposure of
case-control set (years)
1
0
0
1
.0
0.1
=0
x ca
0.01
10
=1
x ca
=1
x ca
0.1
100
00
00
1
Non-Ionising UV Radiation
=1
x ca
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
=0
x ca
Ratio of case exposure to controls' geometric mean
Ionising Radiation
1
10
Geometric mean exposure of
case-control set (years)
Figure A1.5 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Work in fab (left); Work in a building in which fab was situated (centre); Work in other semiconductor factory (right). Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲) are influential cases,
while the solid downward pointing triangles (▼) are influential cases where one of their controls is also influential. These plots are for the
dataset excluding proxy case-control sets.
=1
x ca
=0
x ca
.1
111
0.1
1
Geometric mean exposure of
case-control set (years)
0.01
.0
10
0.1
=0
x ca
.1
1
0
0
=1
x ca
1
.0
0.1
=0
x ca
0.01
1
=1
x ca
=1
x ca
0.1
10
00
00
1
100
=1
x ca
=1
x ca
10
Work at other Semiconductor manufacturer
Ratio of case exposure to controls' geometric mean
100
=0
x ca
Ratio of case exposure to controls' geometric mean
Work in Building in which Fab situated
1
10
Geometric mean exposure of
case-control set (years)
Figure A1.6 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Nightshift (left); Rotational shift (centre); Circadian shift (right). Durations are adjusted for a
10 year latency period. The solid upward pointing triangles (▲) are influential cases, while the solid downward pointing triangles (▼) are
influential cases where one of their controls is also influential. These plots are for the dataset excluding proxy case-control sets.
00
=1
x ca
0
=1
x ca
0.01
0.1
.1
Ratio of case exposure to controls' geometric mean
=1
x ca
112
0.1
=0
x ca
10
1
1
.1
1
10
.0
1
.0
0.1
Geometric mean exposure of
case-control set (years)
100
=0
x ca
0.01
=0
x ca
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
0
0
=0
x ca
1
.0
0.1
Geometric mean exposure of
case-control set (years)
1
=1
x ca
=1
x ca
0.1
10
00
00
1
100
=1
x ca
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
0.01
Circadian Rhythm Disruption
Rotational Shifts
=0
x ca
Ratio of case exposure to controls' geometric mean
Night Work
1
10
Geometric mean exposure of
case-control set (years)
Figure A1.7 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Nightshift non-NSUK (left); Rotational shift non-NSUK (centre); Circadian shift non-NSUK
(right). Durations are adjusted for a 10 year latency period. The solid upward pointing triangles (▲) are influential cases, while the solid
downward pointing triangles (▼) are influential cases where one of their controls is also influential. These plots are for the dataset
excluding proxy case-control sets.
Non-NSUK Circadian Rhythm Disruption
Non-NSUK Rotational Shifts
0
=1
x ca
0.1
.1
Ratio of case exposure to controls' geometric mean
00
=1
x ca
0.01
=0
x ca
113
0.1
1
Geometric mean exposure of
case-control set (years)
1
.0
10
10
=0
x ca
.1
1
100
=1
x ca
=1
x ca
=0
x ca
0.1
1
Geometric mean exposure of
case-control set (years)
0.01
.0
10
0.1
=0
x ca
1
0
=1
x ca
.1
=0
x ca
0.1
1
0.01
1
=1
x ca
0
=1
x ca
0.1
10
00
1
100
=1
x ca
00
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
.0
=0
x ca
Ratio of case exposure to controls' geometric mean
Non-NSUK Night Work
1
10
Geometric mean exposure of
case-control set (years)
Figure A1.8 Plot of the geometric mean of the exposure of the case-control set (years) against the ratio of the exposure of the case to the
geometric mean of the controls’ exposures for: Total duration of employment (left); Total duration of employment at NSUK (centre); Total
duration of employment outside of NSUK (right). Durations are adjusted for a 10 year latency period. The solid upward pointing triangles
(▲) are influential cases, while the solid downward pointing triangles (▼) are influential cases where one of their controls is also
influential. These plots are for the dataset excluding proxy case-control sets.
Employment NSUK
00
=1
x ca
0
=1
x ca
0.01
0.1
.1
Ratio of case exposure to controls' geometric mean
=1
x ca
114
0.1
=0
x ca
10
1
1
.1
1
10
.0
1
.0
0.1
Geometric mean exposure of
case-control set (years)
100
=0
x ca
0.01
=0
x ca
=0
x ca
10
0.1
=1
x ca
=1
x ca
.1
1
Geometric mean exposure of
case-control set (years)
1
0
0
1
.0
0.1
=0
x ca
0.01
10
=1
x ca
=1
x ca
0.1
100
00
00
1
Employment Non-NSUK
=1
x ca
=1
x ca
10
Ratio of case exposure to controls' geometric mean
100
=0
x ca
Ratio of case exposure to controls' geometric mean
Total Employment
1
10
Geometric mean exposure of
case-control set (years)
APPENDIX 2 – WORKER INFORMATION LEAFLET
Research into concerns about cancer at National Semiconductors UK (NSUK) in Greenock
About this leaflet
This leaflet sets out the findings from recent research carried out by the Health and Safety Executive
(HSE) and Institute of Occupational Medicine at the National Semiconductors UK factory in Greenock.
Why have we done this research?
In 2001, HSE published the results of research into concerns about a link between developing cancer
and working at NSUK in Greenock. The research showed that although the overall number of cancers in
the workforce was within the expected range for a workforce like NSUK, there was a possibility that
some cancers could have been associated with work.
Because the findings were not conclusive, HSE, NSUK and the workforce agreed to a further study,
looking particularly at the work done by women who had developed lung, breast and stomach cancer
and men who had developed brain cancer. We also agreed to update the original study because with
more information available the findings would be more reliable.
What did the new research find?
Our new research does not support the earlier concerns about a link between working at NSUK and
developing cancer, especially when taking account of new information about cancer at two IBM
semiconductor factories in America.
However, it is not possible with the type of research we have done to prove that working anywhere is
completely safe.
The new results do show the number of NSUK employees with cancer is within the range we would
expect for a workforce of a similar age and background. And this is also true for each of the individual
types of cancer we studied.
When examining the work done by women with breast cancer and their colleagues, we didn’t find any
notable differences. Also, looking at the work done by people with lung stomach and brain cancer didn’t
produce any important new results – although for these cancers we were unable to make comparisons
with other colleagues.
Other research
Since HSE’s first study was published in 2001, research has been carried out into other companies
which manufactured semiconductors, including two IBM factories in America.
The researchers at IBM decided there was no clear evidence that working there increased the chances
of developing any cancer, including lung, breast, stomach and brain cancer. They did find some
associations with lung, breast and brain cancer but expressed their doubts about the importance of
each of them..
We have carefully considered all the information from the IBM study before reaching our conclusions
about our new study.
More research will be published later in the year in America. HSE will carefully consider these findings.
115
What happens next?
People working at NSUK and their managers must continue to make sure they do their job in a safe
way, following appropriate procedures.
HSE will continue to monitor health and safety in the semiconductor manufacturing industry. If we find
new areas of concern we will advise the industry and expect it to consider changing the way it works.
We have no plans to do more research at NSUK at this stage.
Where can I find more information?
The full scientific report of our research is available online at
http://www.hse.gov.uk/statistics/nsuk/index.htm
If you have any queries about the research, you can call the research team free on
0800 592 450
116
APPENDIX 3 – ADJUSTING THE COHORT MORTALITY AND
CANCER INCIDENCE ANALYSIS FOR DEPRIVATION:
METHODOLOGY AND COMPARISON OF RESULTS
The deprivation adjustment in the updated cohort analysis was carried out using a very similar
approach to that of the original analysis as documented in Appendix 9 of the previous report.
We calculated deprivation adjusted SMRs and SRRs by applying weights to the age-,
calendar time period-, and sex-specific Scottish national mortality and cancer incidence
reference rates. Weights were calculated from national mortality and cancer incidence data by
deprivation and information about the deprivation distribution of NSUK workers derived
from their postcodes. As in the previous analysis we used the Carstairs index of deprivation to
carry out the adjustment i but also compared the results with those adjusted using the newer
Scottish Index of Multiple Deprivation (SIMD) 2004 ii . We also carried out a sensitivity
analysis to check how different the results would be if everyone in the cohort had been in the
most deprived category of the indices.
Weights, wijkl, were calculated as follows:
5
wijkl 

 
n
m 1


ijklm
g im 

pijlm 
5
n
m 1
ijklm
For:
age i
time-period j
sex k
disease l
deprivation quintile m
Where: nijklm
gim
pijkm
(15 5-year categories: 1=15-19, .. , 14=80-84, 15=85+)
(3 categories: 1=1979-83, 2=1989-93, 3=1997-2004*)
(1=male, 2=female)
(the relevant disease categories in the mortality and cancer
incidence analyses)
(1=least deprived, .. , 5=most deprived).
= number of Scottish deaths or cancer registrations in age group i, time period
j, sex k, disease group l, and deprivation quintile m.
= the proportion of NSUK workers in each deprivation quintile m, by sex.
= the proportion of the Scottish population in deprivation quintile m by age,
time period, sex, and deprivation quintile.
*Data for the first two time-periods were not available by SIMD. Adjusted age-, calendar time period-, and sex-specific reference rates were then calculated by multiplying national mortality or cancer registration rates by the appropriate weight, w. Since the calendar time-periods of the weights were different to those of the national rates, the following mapping was used. Weights based on SIMD were only available for the latest time
period (1997-04) and so these were applied to all time periods in the reference rates. i
Carstairs V and Morris R (1991). ‘Deprivation and Health in Scotland’. Aberdeen University Press, Aberdeen. ii
The Scottish Government. Scottish Index of Multiple Deprivation.
http://scotland.gov.uk/Topics/Statistics/SIMD
117
Table A3.1 Mapping of deprivation weight time period to reference rate time period
Carstairs adjustment
SIMD adjustment Time period for
Time period for
Time period for
Time period for reference rate
applied weight
reference rate
applied weight [1]1970-74
[1]1970-74
[1] 1979-83
[2]1975-79
[2]1975-79
[3]1980-84
[3]1980-84 [4]1985-89
[4]1985-89
[3] 1997-04
[2] 1989-93
[5]1990-94
[5]1990-94
[6]1995-99
[6]1995-99
[7]2000-04
[3] 1997-04
[7]2000-04
[8]2005[8]2005-
The deprivation distributions NSUK workers (gim) were obtained for both the Carstairs index
and SIMD based on the postcodes of workers in employment at NSUK on 30 April 1999.
These are shown in the following Table.
Table A3.2 Distribution of NSUK workers by Carstairs index and SIMD, by sex (gim)
Deprivation quintile
1
2
3
4
5
(least deprived . . .
. . . most deprived)
Carstairs index
Males
Females
0.17
0.05
0.07
0.06
0.19
0.13
0.16
0.14
0.42
0.62
SIMD
Males
Females
0.15
0.06
0.26
0.14
0.17
0.13
0.18
0.24
0.25
0.42
Scottish national mortality and cancer registration data were not available by SIMD prior to
1997 and so we had to use the more recent data available according to this index to weight the
rates for earlier time periods. In view of this our preferred methods of adjustment was the
Carstairs index. Alternative SRRs based on SIMD adjusted reference rates were also
calculated in order to explore whether this yielded substantially different results. Since for
both indices the distribution of workers at NSUK was skewed towards being more deprived,
we also tested the maximum effect of the adjustment in this direction by applying weights
based on assuming all workers were in deprivation category 5.
SRRs for men and women by cancer site are shown for these alternative analyses in the
Tables A3.3 and A3.4 along with the unadjusted results.
SRRs adjusted using the Carstairs Index or SIMD were similar. In most cases applying the
deprivation weights has the effect of increasing the size of the reference rates (since for most
cancers higher levels of deprivation are associated with high levels of incidence). This in turn
has the effect of increasing the calculated expected number of cancers among the cohort and
so reducing the SRRs. The deprivation adjustment has the largest effect for lung cancer
among women: the unadjusted SRR is reduced by 26% from 194 to 144 using the Carstairs
index, and by 22% from 194 to 150 using SIMD. When assuming all workers were included
in deprivation category 5, the adjustment based on SIMD tended to have a larger impact on
the SRRs. For example, the lung cancer SRR for women was reduced by 43% from 194 to
110 using SIMD, and by 37% from 194 to 121 using the Carstairs index.
118
Table A3.3 Male cancer registrations by disease group: numbers of cases and SRRs with different deprivation adjustments
SRR (95% confidence interval)
n
Unadjusted
Carstairs1
Carstairs (all
SIMD1
2
deprived)
90.2
(69.1,
116)
(63.7, 107)
62
93.7
(71.9,
120)
83
92.7 (71.1, 119)
All malignant neoplasms
95.8 (71.3, 126)
82.4 (61.3, 108)
97.4 (72.6, 128)
92.3 (68.8, 121)
51
All malignant neoplasms, excluding non-melanoma skin cancer
70.9 (8.6, 256)
47.2 (5.7, 170)
75.1 (9.1, 271)
63.5 (7.7, 229)
2
Malignant neoplasms of the lip, oral cavity and pharynx
126 (70.5, 208)
105 (58.9, 174)
128 (71.7, 211)
120 (67.3, 198)
15
Malignant neoplasms of digestive organs and peritoneum
..
40.4 (1, 225)
..
1
50.8 (1.3, 283)
Malignant neoplasms of the stomach
73.9 (29.7, 152)
49.5 (19.9, 102)
78.3 (31.5, 161)
7
66.5 (26.8, 137)
Malignant neoplasms of respiratory and intrathoracic organs
50.1 (13.7, 128)
33.5 (9.1, 85.8)
4
53 (14.4, 136)
45.1 (12.3, 116)
Malignant neoplasms of trachea, bronchus and lung
..
..
..
0
..
Malignant neoplasm of the pleura
82.2 (41, 147)
82.7 (41.3, 148)
82.2 (41.1, 147)
11
82.4 (41.1, 147)
Malignant neoplasms of other genitourinary organs
94.6 (19.5, 276)
123 (25.4, 360)
92.4 (19.1, 270)
3
100 (20.7, 293)
Malignant melanoma of the skin
80.6 (40.2, 144)
87 (43.4, 156)
79.7 (39.8, 143)
11
81.6 (40.7, 146)
Other malignant neoplasm of the skin
..
..
..
0
..
Malignant neoplasm of the thyroid gland
Malignant neoplasms of the lymphatic and haematopoietic
tissue
Multiple myeloma
Leukaemia
Leukaemia, except chronic lymphatic leukaemia
Malignant neoplasm of the brain and central nervous
Malignant neoplasm of the brain
In situ neoplasms
88.8 (32.6, 193)
6
87.6 (32.2, 191)
349 (42.2, 1260)
2
346 (41.8, 1250)
..
0
..
..
0
..
199 (54.3, 511)
4
203 (55.2, 519)
206 (56, 526)
4
209 (57, 535)
- (0, 144)
0
- (0, 148)
.. SRR not shown where both observed and expected cancer registrations <2
1
Derived using the Carstairs/SIMD distribution of NSUK workers from Table A3.2
2
Assuming all workers in Carstairs or SIMD deprivation category 5.
119
85 (31.2, 185)
340 (41.1, 1230)
..
..
216 (58.9, 554)
225 (61.3, 576)
- (0, 160)
88.3 (32.4, 192)
341 (41.3, 1230)
..
..
199 (54.2, 509)
205 (55.9, 525)
- (0, 144)
SIMD (all
deprived)2
82.7 (63.4, 106)
80.8 (60.2, 106)
45.9 (5.6, 166)
106 (59.3, 175)
37.1 (0.9, 207)
44.7 (18, 92)
30.3 (8.3, 77.7)
..
83.1 (41.5, 149)
125 (25.8, 366)
91.7 (45.8, 164)
..
82.5 (30.3, 180)
301 (36.5, 1090)
..
..
219 (59.6, 560)
224 (60.9, 572)
- (0, 153)
Table A3.4 Female cancer registrations by disease group: numbers of cases and SRRs with different deprivation adjustments
SRR (95% confidence interval)
1
n
Unadjusted
Carstairs
SIMD1
Carstairs (all
2
deprived)
122 103 (85.8, 123)
102 (84.9, 122)
102 (84.8, 122)
101 (84.1, 121)
All malignant neoplasms
99.7 (81.6, 121)
105 104 (84.9, 126)
101 (82.8, 123)
101 (82.8, 123)
All malignant neoplasms, excluding non-melanoma skin cancer
140 (28.9, 410)
155 (32, 453)
159 (32.9, 465)
3 183 (37.7, 534)
Malignant neoplasms of the lip, oral cavity and pharynx
120 (67.4, 199)
118 (66, 194)
15 126 (70.6, 208)
121 (67.7, 200)
Malignant neoplasms of digestive organs and peritoneum
315 (102, 736)
283 (91.8, 660)
5
370 (120, 863)
312 (101, 729)
Malignant neoplasms of the stomach
139 (79.2, 225)
111 (63.3, 180)
16
179 (102, 291)
132 (75.5, 215)
Malignant neoplasms of respiratory / intrathoracic organs
150 (86, 244)
121 (69.3, 197)
16
194 (111, 315)
144 (82.3, 234)
Malignant neoplasms of trachea, bronchus and lung
..
..
..
0
..
Malignant neoplasm of the pleura
(28.6,
103)
57.3
11
66.9
(33.4,
120)
60.6
(30.3,
108)
60.8
(30.4,
109)
Malignant neoplasms of other genitourinary organs
116 (37.7, 271)
5
82 (26.6, 191)
99.4 (32.3, 232)
95.7 (31.1, 223)
Malignant melanoma of the skin
113 (65.6, 180)
17 100 (58.5, 161)
109 (63.2, 174)
107 (62.3, 171)
Other malignant neoplasm of the skin
128 (93.3, 170)
46 116 (85.2, 155)
123 (89.7, 163)
120 (88.2, 161)
Malignant neoplasm of the female breast
55.2 (6.7, 200)
2
54.9 (6.6, 199)
55.3 (6.7, 200)
55.2 (6.7, 199)
Malignant neoplasm of the uterus
73.9 (20.1, 189)
4 71.8 (19.6, 184)
70.9 (19.3, 182)
72.8 (19.8, 187)
Malignant neoplasm of the ovary
..
..
..
0
..
Malignant neoplasm of the thyroid gland
64.6 (17.6, 166)
69 (18.8, 177)
4 64.2 (17.5, 164)
66.6 (18.1, 171)
Malignant neoplasms of the lymphatic and haematopoietic tissue
..
..
..
0
..
Multiple myeloma
..
..
1
..
..
Leukaemia
..
..
1
..
..
Leukaemia, except chronic lymphatic leukaemia
0
..
..
..
..
Malignant neoplasm of the brain and central nervous
..
..
..
0
..
Malignant neoplasm of the brain
80.2 (63.1, 101)
75
83.9 (66, 105)
81.2 (63.9, 102)
77.1 (60.7, 96.7)
In situ neoplasms
.. SRR not shown where both observed and expected cancer registrations <2
1
Derived using the Carstairs/SIMD distribution of NSUK workers from Table A3.2
2
Assuming all workers in Carstairs or SIMD deprivation category 5.
120
SIMD (all
deprived)2
99.3 (82.5, 119)
97 (79.3, 117)
127 (26.1, 370)
113 (63.5, 187)
254 (82.3, 592)
101 (57.5, 163)
110 (63, 179)
..
54.3 (27.1, 97.2)
122 (39.6, 285)
115 (66.9, 184)
127 (92.6, 169)
55.7 (6.7, 201)
71.5 (19.5, 183)
..
65.9 (18, 169)
..
..
..
..
..
66.8 (52.6, 83.7)
APPENDIX 4 – JOB EXPOSURE MATRIX (JEM)
List of items
Table A4.1 NSUK Shift Work Exposure Matrix
Table A4.2 Non-NSUK Shift Work Exposure Matrix
Table A4.3 NSUK Building Area Fab-Related Work
Table A4.4 NSUK Fab work – Job Title
Table A4.5 NSUK Processes with Radiation
Table A4.6 NSUK Carcinogen Processes
Table A4.7 NSUK Groups of Agents Processes
121
Table A4.1 NSUK Shift Work Exposure Matrix
Que.
Coding
scheme
8-hour static day or office hours (7am-3pm;
601
8.30am-5pm 8-hour static swing/back shift (3pm-11pm)
602
8 hour static night shift (11pm-7am)
603
8 hour rotating shifts (one week of each 604
day, swing, nights) ‘Weekend warrior’ static day shift (e.g.
605
7am-7pm)
‘Weekend warrior’ static night shift (e.g.
606
7pm-7am)
‘Weekend warrior’ rotating day and night
607
shifts
12 hour static day shift
608
12 hour static night shift
609
12 hour rotating day / night shifts (e.g. two
610
weeks days; two weeks nights
Unknown
611
Other (please specify)
Free
text
Involves
night
work?
2
Involves
rotational
shifts?
2
Disrupt
circadian
rhythm?
2
2
1
1
2
2
1
2
1
1
2
2
2
1
2
1
1
1
1
2
1
1
2
2
1
2
1
1
3
Assessed
individually
3
Assessed
individually
3
Assessed
individually
Coding: 1=yes; 2=no; 3=unknown
Table A4.2 Non-NSUK Shift Work Exposure Matrix
Flash card I
Day shift, for example, 7-3; 8.30-5
Back shift / swing shift, for example, 2­
10, 3-11
Night shift, 10-6, 11-7
Rotating day and back shift (but no night
shift)
Rotating day or swing shift and night shift
Don’t know
Some other shift pattern
101
102
2
2
2
2
Likely to
disrupt
circadian
rhythm?
2
2
103
104
1
2
2
1
1
1
105
106
Free text
1
3
Assessed
individually
1
3
Assessed
individually
1
3
Assessed
individually
Que.
Coding
scheme
Coding: 1=yes; 2=no; 3=unknown.
122
Involves
night
work?
Involves
rotational
work?
Table A4.3 NSUK Building Area Fab-Related Work
Building / area
Original building prior to fire (1976) – non fab area
Original building prior to fire (1976) – fab area (3” MOS)
Original building prior to fire (1976) – fab area (3” TTL)
Original building prior to fire (1976) – fab area (3” LIC)
Original building prior to fire (1976) – fab area
Original building prior to fire (1976) – non-fab and fab areas
Original building prior to fire (1976) - area unknown
Building A – non fab areas only
Building A - Fab (4” LIC)
Building A - Fab (4” logic)
Building A- Fab (4” after LIC and logic merged)
Building A - Fab (4” MOS)
Building A – fab, division unknown
Building A – Assembly
Building A - non-fab and fab areas
Building A - area unknown
Building B – Assembly
Building B – Mil/aero (test and high reliability)
Building B – Quality assurance
Building B – Offices
Building B – Stores
Building B - area unknown
Building C / existing building – non-fab area
Building C / existing building – non-fab and fab areas
Building C / existing building – Fab 2 (4” MOS wafers)
Building C / existing building – Fab 3 (6” wafers)
Building C / existing building – Fab (6” fab after fabs 1&2 closed)
Building C / existing building – Fab, division unknown
Building C / existing building – Quality assurance
Building C - area unknown
Other NSUK plant e.g. USA - non fab area
Other NSUK plant e.g. USA - fab area
Other NSUK plant e.g. USA - non-fab and fab areas
Other NSUK plant e.g. USA
Non fab area (general)
Fab (general)
Non-fab and fab area (general)
Unknown
All Buildings
Building C all fab areas
Portakabin near main building
123
Que.
Coding
Scheme
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
Fab related
work in this
area?
2
1
1
1
1
1
3
2
1
1
1
1
1
2
1
3
2
2
2
2
2
2
2
1
1
1
1
1
2
3
2
1
1
3
2
1
1
3
1
1
2
Table A4.4 NSUK Fab Work – Job Title
Job Title Fab operator
Fab technician
Operating technician
Process operator
Manufacturing technician
Grade 1 operator / technician
Grade 2 operator / technician
Grade 3 operator / technician
Grade 4-5 (training specialist)
Grade 6 production specialist
Lab technician assistant aka acid tech assistant
Lab technician / lab tech / acid tech
Deposition operator
Diffusion operator
Masking operator
Photo / photolithography operator
Etch operator
Metals / metallization operator
High vac operator
EM2 technicians / engineers
Engineering technician
Fab area domestic / hygiene technician
Industrial engineer
Plant maintenance technician / engineers
Facilities maintenance technician / engineers
Process technician / engineers
Supervisor
Administration staff
Assembly operator
Cleaner
Failure analysis operator
Health and safety officer
Kitchen / canteen staff
Mil / Aero operator
Nurse
Occupational hygienist
Personnel
Quality control / assurance
Receptionist
Store personnel
Tester
Unknown Wafer Inspection
Inspection Trainer
Accountant
USA Plant Manager
Health & Safety Rep
Backcoating
124
Que. Coding
Scheme
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
Fab work involved
for this job title?
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
3
1
1
2
1
1
1
Table A4.5 NSUK Processes with Radiation
Align / Aligning
Critical dimensions
Develop
Develop inspection
Final inspection
Mask control
Spin / spinner / spin track
Vapour prime
922 stripper
Aluminium etch (wet etch)
Asher
Dry etch
Dry strips
Mask cleaning
Metal etch (wet etch)
Nitride strip
Oxide etch (wet etch)
Plasma etch
Posistrip 830 / Posistrip
Sulphuric strip
Titanium tungsten etch (wet etch)
Vapox etch (wet etch)
Wet etch (general)
Wet strips (general)
Antimony implant drive
Antimony trioxide collector
furnace
Furnace (name provided by
interviewee)
Furnaces (general)
POCl furnaces
Rapid Thermal Anneal
Emptying antimony waste bin
Profiling furnaces
Chemical Vapour Deposition
(nitride / passivation)
Epitaxial process / epi
Vapox
Vapox reactor clean
Evaporators
Sputters
Implant / implantors / ion
implant(ors)
Backcoating
Backlap / backgrind
Cardex / material handling
Laserscribe
Sort / probe
Non-ionising
Ionising
Non-ionising
Que.
Coding Radiation radiation (RF radiation (UV
source only)
source only)
Scheme
501
2
2
1
502
2
2
1
503
2
2
1
504
2
2
1
505
2
2
1
506
2
2
2
507
2
2
2
508
2
2
2
509
2
2
1
510
2
2
1
511
2
1
1
512
2
1
1
513
2
1
1
514
2
2
1
515
2
2
1
516
2
2
1
517
2
2
1
518
2
1
1
519
2
2
1
520
2
2
1
521
2
2
1
522
2
2
1
523
2
2
1
524
2
2
1
525
2
2
1
526
2
2
1
527
2
2
1
528
529
530
531
532
533
2
2
2
2
2
2
2
2
2
2
2
1
1
1
1
2
2
1
534
535
536
537
538
539
2
1
2
2
1
1
1
2
2
1
1
2
1
1
2
2
1
2
540
541
542
543
544
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
125
Non-ionising
Que.
Ionising
Non-ionising
Coding Radiation radiation (RF radiation (UV
source only)
source only)
Scheme
Wafer sort / probe
545
2
2
1
1
Wafer cleans (general)
546
2
2
2
General fab room cleaning
547
2
2
2
Replenishment of wet decks
548
2
2
2
Element replacement on wet deck
549
2
2
2
Manifold burning / cleaning
550
2
2
2
Scrubber cleans
551
2
2
SIRTLE etch mix
552
2
2
2
Catch cup cleans
553
2
2
2
Emptying antimony waste bin
554
2
2
2
Profiling furnaces
555
2
2
2
Quartzware cleans
556
2
2
2
Cleaning epitaxial reactor
557
2
2
2
Vapox reactor clean
558
2
2
2
Implant gas bottle change
559
1
2
2
Implant source building
560
1
2
2
Assembly
561
2
2
1
Die attach
562
2
2
2
Die cutting
563
2
2
2
Electrical test
564
2
2
2
Failure analysis
565
1
2
2
Fine or final leak testing / tracer
566
1
2
2
flow
Gross leak testing
567
2
2
2
Lead bonding
568
2
2
2
Mark and bake
569
2
2
2
Sealing
570
2
2
2
Tracer flow / fine or final leak
571
1
2
2
testing
3
3
3
Unknown
572
Gold Room Tasks
573
2
2
3
Administration
574
2
2
2
Catering
575
2
2
2
Finance
576
2
2
2
Inspection
577
2
2
1
Fab room supervisory tasks
578
2
2
2
Offline training
579
2
2
2
Shipping (internal and external)
580
2
2
2
Health and safety representative
581
2
2
2
tasks
Occupational health service
582
2
2
2
On-line training (diffusion /
583
1
1
1
deposition)
Various
photolithography
584
2
2
1
engineering tasks (align, develop
and test)
General equipment maintenance
585
1
1
1
and testing
Maintenance of die attach
586
2
2
2
equipment
126
Que.
Ionising
Non-ionising
Non-ionising
Coding Radiation radiation (RF radiation (UV
Scheme
source only)
source only)
General masking processes
587
2
1
1
2
Cleaning
588
2
2
2
Generally office based but
589
2
2
travelled throughout all area of
the plant
2
Moving batches of wafers into
590
2
2
diffusion
Wafer Test Engineer
591
2
2
1
Test, high reliability, sputter
592
1
1
1
engineer
Isolation furnace
593
2
2
1
Emitter furnace
594
2
2
1
Alloy Furnace
595
2
2
1
Initials, Base, Collector Furnace
596
2
2
1
Arsine furnace
597
2
2
1
127
Table A4.6 NSUK Carcinogen Processes
Que.
Antimony
Coding trioxide
Scheme
Align / Aligning
Critical dimensions
Develop
Develop inspection
Final inspection
Mask control
Spin / spinner / spin track
Vapour prime
922 stripper
Aluminium etch (wet etch)
Asher
Dry etch
Dry strips
Mask cleaning
Metal etch (wet etch)
Nitride strip
Oxide etch (wet etch)
Plasma etch
Posistrip 830 / Posistrip
Sulphuric strip
Titanium tungsten etch (wet etch)
Vapox etch (wet etch)
Wet etch (general)
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
Arsenic and
arsenical
compounds,
including
arsine
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
128
Asbestos
Carbon Ceramic
Chromium Sulphuric Trichloro(in
tetrafibre
trioxide
acid mist ethylene
buildings) chloride “Kaowool” and
chromic
acid
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
2
2
1
2
2
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
1
2
2
1
2
2
2
2
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
Antimony
Que.
Coding trioxide
Scheme
Wet strips (general)
Antimony implant drive
Antimony trioxide collector furnace
Furnace (name provided by
interviewee)
524
525
526
527
Furnaces (general)
POCl furnaces
Rapid Thermal Anneal
Emptying antimony waste bin
Profiling furnaces
Chemical Vapour Deposition (nitride /
passivation)
Epitaxial process / epi
Vapox
Vapox reactor clean
Evaporators
Sputters
Implant / implantors / ion implant(ors)
Backcoating
Backlap / backgrind
Cardex / material handling
Laserscribe
Sort / probe
Wafer sort / probe
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
Arsenic and
arsenical
compounds,
including
arsine
2
2
1
2
1
2
Dependent Dependent
on furnace on furnace
name
name
1
1
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
1
2
2
2
2
1
2
2
2
2
2
2
129
Carbon Ceramic
Chromium Sulphuric TrichloroAsbestos
tetra(in
fibre
trioxide
acid mist ethylene
buildings) chloride “Kaowool” and
chromic
acid
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
1
1
1
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
1
1
2
1
1
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
Que.
Antimony
Coding trioxide
Scheme
Wafer cleans (general)
General fab room cleaning
Replenishment of wet decks
Element replacement on wet deck
Manifold burning / cleaning
Scrubber cleans
SIRTLE etch mix
Catch cup cleans
Emptying antimony waste bin
Profiling furnaces
Quartzware cleans
Cleaning epitaxial reactor
Vapox reactor clean
Implant gas bottle change
Implant source building
Assembly
Die attach
Die cutting
Electrical test
Failure analysis
Fine or final leak testing / tracer flow
Gross leak testing
Lead bonding
Mark and bake
Sealing
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
2
2
2
2
2
2
2
2
1
2
1
2
2
1
1
2
2
2
2
2
2
2
2
2
2
Arsenic and
arsenical
compounds,
including
arsine
2
2
2
2
2
2
2
2
2
2
1
1
2
1
1
2
2
2
2
2
2
2
2
2
2
130
Chromium Sulphuric TrichloroCarbon Ceramic
Asbestos
acid mist ethylene
trioxide
fibre
tetra(in
buildings) chloride “Kaowool” and
chromic
acid
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
1
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
Antimony
Que.
Coding trioxide
Scheme
Tracer flow / fine or final leak testing
Unknown
Gold Room Tasks
Administration
Catering
Finance
Inspection
Fab room supervisory tasks
Offline training
Shipping (internal and external)
Health and safety representative tasks
Occupational health service
On-line training (diffusion / deposition)
Various photolithography engineering
tasks (align, develop and test)
General equipment maintenance and
testing
Maintenance of die attach equipment
General masking processes
Cleaning
Generally office based but travelled
throughout all area of the plant
Moving batches of wafers into diffusion
Wafer Test Engineer
Test, high reliability, sputter engineer
Chromium Sulphuric TrichloroCarbon Ceramic
Asbestos
acid mist ethylene
trioxide
fibre
tetra(in
buildings) chloride “Kaowool” and
chromic
acid
2
2
2
2
2
2
3
3
3
3
3
3
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
1
2
1
2
2
2
2
2
2
2
571
572
573
574
575
576
577
578
579
580
581
582
583
584
2
3
3
2
2
2
2
2
2
2
2
2
1
2
Arsenic and
arsenical
compounds,
including
arsine
2
3
3
2
2
2
2
2
2
2
2
2
1
2
585
2
2
2
2
2
2
2
2
586
587
588
589
2
2
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
590
591
592
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
131
Antimony
Que.
Coding trioxide
Scheme
Isolation furnace
Emitter furnace
Alloy Furnace
Initials, Base, Collector Furnace
Arsine furnace
593
594
595
596
597
2
2
2
1
2
Arsenic and
arsenical
compounds,
including
arsine
2
1
2
1
1
132
Chromium Sulphuric TrichloroCarbon Ceramic
Asbestos
acid mist ethylene
trioxide
fibre
tetra(in
buildings) chloride “Kaowool” and
chromic
acid
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
1
2
Table A4.7 NSUK Groups of Agents Processes
Align / Aligning
Critical dimensions
Develop
Develop inspection
Final inspection
Mask control
Spin / spinner / spin track
Vapour prime
922 stripper
Aluminium etch (wet etch)
Asher
Dry etch
Dry strips
Mask cleaning
Metal etch (wet etch)
Nitride strip
Oxide etch (wet etch)
Plasma etch
Posistrip 830 / Posistrip
Sulphuric strip
Titanium tungsten etch (wet etch)
Vapox etch (wet etch)
Wet etch (general)
Wet strips (general)
Antimony implant drive
Antimony trioxide collector furnace
Furnace (name provided by
interviewee)
Furnaces (general)
POCl furnaces
Rapid Thermal Anneal
Emptying antimony waste bin
Profiling furnaces
Chemical Vapour Deposition (nitride /
passivation)
Epitaxial process / epi
Vapox
Vapox reactor clean
Evaporators
Sputters
Implant / implantors / ion implant(ors)
Backcoating
Backlap / backgrind
Cardex / material handling
Laserscribe
Sort / probe
Que. Coding
Scheme
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
Solvents Acids Toxic gases
1
2
1
2
2
2
1
1
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
1
2
2
2
1
1
1
1
2
1
1
1
1
1
1
1
1
1
528
529
530
531
532
533
2
2
2
2
2
2
1
1
2
2
2
1
534
535
536
537
538
539
540
541
542
543
544
2
2
2
2
2
2
2
2
2
2
2
1
1
2
1
1
1
1
1
2
1
2
133
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
1
2
2
2
2
2
2
2
2
Dependent on
furnace name
1
2
2
2
2
1
1
1
2
2
1
2
2
2
2
2
Wafer sort / probe
Wafer cleans (general)
General fab room cleaning
Replenishment of wet decks
Element replacement on wet deck
Manifold burning / cleaning
Scrubber cleans
SIRTLE etch mix
Catch cup cleans
Emptying antimony waste bin
Profiling furnaces
Quartzware cleans
Cleaning epitaxial reactor
Vapox reactor clean
Implant gas bottle change
Implant source building
Assembly
Die attach
Die cutting
Electrical test
Failure analysis
Fine or final leak testing / tracer flow
Gross leak testing
Lead bonding
Mark and bake
Sealing
Tracer flow / fine or final leak testing
Unknown
Gold Room Tasks
Administration
Catering
Finance
Inspection
Fab room supervisory tasks
Offline training
Shipping (internal and external)
Health and safety representative tasks
Occupational health service
On-line training (diffusion / deposition)
Various photolithography engineering
tasks (align, develop and test)
General equipment maintenance and
testing
Maintenance of die attach equipment
General masking processes
Cleaning
Generally office based but travelled
throughout all area of the plant
Que. Coding
Scheme
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
Solvents Acids Toxic gases
2
2
1
2
2
1
3
2
1
2
2
2
1
2
2
1
1
1
2
2
2
2
2
1
2
2
2
3
3
2
2
2
2
2
2
2
2
2
1
2
2
1
2
1
1
2
3
1
1
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
3
3
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
3
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
3
3
2
2
2
2
2
2
2
2
2
1
2
585
2
2
2
586
587
588
589
2
1
1
2
2
2
2
2
2
2
2
2
134
Moving batches of wafers into diffusion
Wafer Test Engineer
Test, high reliability, sputter engineer
Isolation furnace
Emitter furnace
Alloy Furnace
Initials, Base, Collector Furnace
Arsine furnace
Que. Coding
Scheme
590
591
592
593
594
595
596
597
135
Solvents Acids Toxic gases
2
2
2
2
2
2
2
2
2
2
2
1
1
1
1
1
2
2
2
1
1
2
1
1
Health and Safety
Executive
A further study of cancer among the
current and former emp
loyees of Nat
ional
employees
National
Semiconductor (UK) Ltd., Greenock
aph
aph
aph
aph
aph
aph
20030.01 cover final.indd 4
8/16/10 4:17:07 PM