Environment and Breast Cancer: Science Review

Mortality and exposure response among 14,458 electrical capacitor manufacturing workers exposed to polychlorinated biphenyls (PCBs)
Prince, M. M., Ruder, A. M., Hein, M. J., Waters, M. A., Whelan, E. A., Nilsen, N., Ward, E. M., Schnorr, T. M., Laber, P. A., Davis-King, K. E. Environ Health Perspect. 2006. 114:10, 1508-14.

Topic area
Environmental pollutant - PCBs Occupation
Environmental pollutant - PCBs Occupation
Study design
Follow-up of retrospective cohort
Follow-up of retrospective cohort
Funding agency
NIOSH
NIOSH

Study Participants
Number of Cases
111
111
Menopausal Status
The menopausal status of women included in this study is listed here.
No analysis based on menopausal status
Number in Cohort
Cohort: 7,961 women
Cohort: 7,961 women
Cohort participation rate
Not applicable. This study was records-based.
Not applicable. This study was records-based.
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
This National Institute for Occupational Safety and Health (NIOSH) cohort consisted of 14,458 workers (7,961 women) employed at least 90 days in electrical capacitor manufacturing at a New York plant between 1946-1977 or at a Massachusetts plant between 1939-1976. Mortality was followed through 1998 using records from SSA, IRS, NDI, US postal service and credit bureaus. Cause of death identified from NDI plus and death certificates with review by nosologist. NDI does not include deaths before 1979, so workers lost to follow-up before that year were censored at date last observed.
Comment about participation selection
This occupational cohort uniquely looks at workers exposed to PCBs >20 years ago, allowing for a latency period that is consistent with that of breast cancer. This analysis include all workers at the two plants, as compared to the another report, which was limited to highly exposed workers, also published by Prince et al. in 2006 (Environ Health).
This occupational cohort uniquely looks at workers exposed to PCBs >20 years ago, allowing for a latency period that is consistent with that of breast cancer. This analysis include all workers at the two plants, as compared to the another report, which was limited to highly exposed workers, also published by Prince et al. in 2006 (Environ Health).

Exposure Investigated
Exposures investigated
Ever worked for β₯90 days in one of the two electrical capacitor manufacturing plants. Plant-specific job exposure matrices were developed using job descriptions, product factors, process information, PCB usage eras, industrial hygiene air sampling data,
Ever worked for β₯90 days in one of the two electrical capacitor manufacturing plants. Plant-specific job exposure matrices were developed using job descriptions, product factors, process information, PCB usage eras, industrial hygiene air sampling data,
How exposure was measured
Job history Environmental sample Other: Job exposure matrix (JEM)
Job history Environmental sample Other: Job exposure matrix (JEM)
Exposure assessment comment
The following commercial PCB mixtures were used at both plants: Aroclor 1254 (54% chlorine, phased out in 1950s at plant 1), Aroclor 1242 (42% chlorine, first used at plant 1 in 1971), and Aroclor 1016 (41% chlorine). There was likely overlap between the types of Aroclor used at a particular time, and less chlorinated versions were used in more recent years. No information available about dates of use at plant 2.
The following commercial PCB mixtures were used at both plants: Aroclor 1254 (54% chlorine, phased out in 1950s at plant 1), Aroclor 1242 (42% chlorine, first used at plant 1 in 1971), and Aroclor 1016 (41% chlorine). There was likely overlap between the types of Aroclor used at a particular time, and less chlorinated versions were used in more recent years. No information available about dates of use at plant 2.
Breast cancer outcome investigated
Mortality
Mortality
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Age, calendar year
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked Yes. No, if not.
No
Strength of associations reported
Breast cancer mortality compared to US population:
Overall: SMR 0.96 (95% CI 0.79-1.15)
Plant 1 (New York): SMR 0.91 (95% CI 0.65-1.24)
Plant 2 (Massachusetts): SMR 0.98 (95% CI 0.77-1.23)
Cumulative exposure among PCB-exposed workers employed β₯90 days (ref = Q1 (<150 unit-years)):
Q2 (150 β <620): IRR 1.09 (95% CI 0.64β1.85)
Q3 (620 β <2300): IRR 0.79 (95% CI: 0.44β1.43)
Q4 (β₯ 2,300): IRR 1.32 (95% CI 0.75β2.30)
Q4 (β₯ 2,300), 10-year lag: IRR 1.44 (95% CI 0.82-2.52)
Q4 (β₯ 2,300), 20-year lag: IRR 1.25 (95% CI 0.68-2.30)
Breast cancer mortality compared to US population:
Overall: SMR 0.96 (95% CI 0.79-1.15)
Plant 1 (New York): SMR 0.91 (95% CI 0.65-1.24)
Plant 2 (Massachusetts): SMR 0.98 (95% CI 0.77-1.23)
Cumulative exposure among PCB-exposed workers employed β₯90 days (ref = Q1 (<150 unit-years)):
Q2 (150 β <620): IRR 1.09 (95% CI 0.64β1.85)
Q3 (620 β <2300): IRR 0.79 (95% CI: 0.44β1.43)
Q4 (β₯ 2,300): IRR 1.32 (95% CI 0.75β2.30)
Q4 (β₯ 2,300), 10-year lag: IRR 1.44 (95% CI 0.82-2.52)
Q4 (β₯ 2,300), 20-year lag: IRR 1.25 (95% CI 0.68-2.30)
Results Comments
Sub-analyses by cumulative exposure category were limited by small numbers and the lack individual information on common risk factors may result in residual confounding. Concomitant exposures to other chemicals, including TCE and metals, were evaluated and discussed in the context of liver cancer, but not breast cancer. Five hundred and fifty workers (# of female workers not specified) were known to be potentially exposed to TCE due to work in degreasing activities, though authors note that plant 2 did not have sufficient job history data available to classify potential TCE exposure before 1950.
Sub-analyses by cumulative exposure category were limited by small numbers and the lack individual information on common risk factors may result in residual confounding. Concomitant exposures to other chemicals, including TCE and metals, were evaluated and discussed in the context of liver cancer, but not breast cancer. Five hundred and fifty workers (# of female workers not specified) were known to be potentially exposed to TCE due to work in degreasing activities, though authors note that plant 2 did not have sufficient job history data available to classify potential TCE exposure before 1950.

Abstract
BACKGROUND: We expanded an existing cohort of workers (n = 2,588) considered highly exposed to polychlorinated biphenyls (PCBs) at two capacitor manufacturing plants to include all workers with at least 90 days of potential PCB exposure during 1939-1977 (n = 14,458). Causes of death of a priori interest included liver and rectal cancers, previously reported for the original cohort, and non-Hodgkin lymphoma (NHL), melanoma, and breast, brain, intestine, stomach, and prostate cancers, based on other studies. METHODS: We ascertained vital status of the workers through 1998, and cumulative PCB exposure was estimated using a new job exposure matrix. Analyses employed standardized mortality ratios (SMRs; U.S., state, and county referents) and Poisson regression modeling. RESULTS: Mortality from NHL, melanoma, and rectal, breast, and brain cancers were neither in excess nor associated with cumulative exposure. Mortality was not elevated for liver cancer [21 deaths; SMR 0.89; 95% confidence interval (CI), 0.55-1.36], but increased with cumulative exposure (trend p-value = 0.071). Among men, stomach cancer mortality was elevated (24 deaths; SMR 1.53; 95% CI, 0.98-2.28) and increased with cumulative exposure (trend p-value = 0.039). Among women, intestinal cancer mortality was elevated (67 deaths; SMR 1.31; 95% CI, 1.02-1.66), especially in higher cumulative exposure categories, but without a clear trend. Prostate cancer mortality, which was not elevated (34 deaths; SMR 1.04; 95% CI, 0.72-1.45), increased with cumulative exposure (trend p-value = 0.0001). CONCLUSIONS: This study corroborates previous studies showing increased liver cancer mortality, but we cannot clearly associate rectal, stomach, and intestinal cancers with PCB exposure. This is the first PCB cohort showing a strong exposure-response relationship for prostate cancer mortality.
BACKGROUND: We expanded an existing cohort of workers (n = 2,588) considered highly exposed to polychlorinated biphenyls (PCBs) at two capacitor manufacturing plants to include all workers with at least 90 days of potential PCB exposure during 1939-1977 (n = 14,458). Causes of death of a priori interest included liver and rectal cancers, previously reported for the original cohort, and non-Hodgkin lymphoma (NHL), melanoma, and breast, brain, intestine, stomach, and prostate cancers, based on other studies. METHODS: We ascertained vital status of the workers through 1998, and cumulative PCB exposure was estimated using a new job exposure matrix. Analyses employed standardized mortality ratios (SMRs; U.S., state, and county referents) and Poisson regression modeling. RESULTS: Mortality from NHL, melanoma, and rectal, breast, and brain cancers were neither in excess nor associated with cumulative exposure. Mortality was not elevated for liver cancer [21 deaths; SMR 0.89; 95% confidence interval (CI), 0.55-1.36], but increased with cumulative exposure (trend p-value = 0.071). Among men, stomach cancer mortality was elevated (24 deaths; SMR 1.53; 95% CI, 0.98-2.28) and increased with cumulative exposure (trend p-value = 0.039). Among women, intestinal cancer mortality was elevated (67 deaths; SMR 1.31; 95% CI, 1.02-1.66), especially in higher cumulative exposure categories, but without a clear trend. Prostate cancer mortality, which was not elevated (34 deaths; SMR 1.04; 95% CI, 0.72-1.45), increased with cumulative exposure (trend p-value = 0.0001). CONCLUSIONS: This study corroborates previous studies showing increased liver cancer mortality, but we cannot clearly associate rectal, stomach, and intestinal cancers with PCB exposure. This is the first PCB cohort showing a strong exposure-response relationship for prostate cancer mortality.
Author address
National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Cincinnati, Ohio 45226, USA.
National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Cincinnati, Ohio 45226, USA.
Reviewers Comments
Mortality is not a sensitive measure of breast cancer risk. SMRs that use the general population for comparison may be biased downward due to the healthy worker effect.
Mortality is not a sensitive measure of breast cancer risk. SMRs that use the general population for comparison may be biased downward due to the healthy worker effect.