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Background: Ethylene oxide (ETO) is a sterilant gas considered to be a human carcinogen, due primarily to excess hematopoietic cancer in exposed cohorts. ETO causes mammary tumors in mice, and has been associated with breast cancer incidence in one small epidemiologic study., Methods: We have studied breast cancer incidence in a cohort of 7576 women employed for at least one year and exposed for an average 10.7 years while working in commercial sterilization facilities. Breast cancer incidence (n = 319) was ascertained via interview, death certificates, cancer registries, and medical records. Interviews were obtained for 68% of the cohort., Results: The standardized incidence ratio (SIR) for incident breast cancer in the whole cohort using external referent rates (SEER) was 0.87 (0.77-0.97). The SIR for those in the top quintile of cumulative exposure, with a 15 year lag, was 1.27 (0.94-1.69), with a positive trend of increasing SIR with increasing exposure (p = 0.002). SIRs are underestimated because breast cancer incidence in the whole cohort was under-ascertained, due to incomplete response and lack of complete coverage by state cancer registries. In internal nested case-control analyses of those with interviews (complete cancer ascertainment), controlling for reproductive risk factors, a positive exposure-response was found with the log of cumulative exposure with a 15-year lag (p = 0.0005). The odds ratio by quintile of cumulative exposure were 1.00 (0 exposure due to 15 year lag), 1.06, 0.99, 1.24, 1.42, and 1.87., Conclusions: Our data suggest that ETO is associated with breast cancer, but a causal interpretation is weakened due to some inconsistencies in exposure-response trends and possible biases due to non-response and incomplete cancer ascertainment.

Low-levels of dioxin cause cancer in animals. In 1997 dioxin was found to be a human carcinogen by the International Agency for Research on Cancer, based largely on four studies of industrial workers exposed to high levels. Recently there has been interest in estimating human cancer risk at low level environmental exposures. Here we review quantitative exposure-response analyses and risk assessment for low environmental levels based on the largest existing cohort of workers exposed to dioxin (the U.S. NIOSH cohort). We estimate that doubling background levels of exposure, which may occur for example by eating a lot of fish which have accumulated dioxin, will increase lifetime risk of cancer death by 0.1 to 1.0%. In the US the background risk of cancer death by age 75 is 12%, so doubling background levels of dioxin exposure would increase this lifetime risk to somewhere between 12.1 and 13.0%. Our results agree broadly with results from a German cohort, which is the only other cohort for which a quantitative risk assessment has been conducted.

Although vinyl chloride is an established cause of liver angiosarcoma, the evidence is inconclusive on whether it also causes other neoplastic and nonneoplastic chronic liver diseases as well as neoplasms in other organs. Furthermore, the shape of the dose-response relation for angiosarcoma is uncertain. We have extended for approximately 8 years the mortality and cancer incidence follow-up of 12,700 male workers in the vinyl chloride industry in four European countries. All-cause mortality was lower than expected, whereas cancer mortality was close to expected. A total of 53 deaths from primary liver cancer (standardized mortality ratio 2.40, 95% confidence interval = 1.80-3.14) and 18 incident cases of liver cancer were identified, including 37 angiosarcomas, 10 hepatocellular carcinomas, and 24 liver cancers of other and unknown histology. In Poisson regression analyses we observed a marked exposure response for all liver cancers, angiosarcoma, and hepatocellular carcinoma. The exposure-response trend estimated for liver cancer in analyses restricted to cohort members with cumulative exposures of <1,500 parts per million-years was close to that estimated for the full cohort (relative risk of 2.0 per logarithmic unit of cumulative dose). No strong relation was observed between cumulative vinyl chloride exposure and other cancers. Although cirrhosis mortality was decreased overall, there was a trend with cumulative exposure.

Background: In 1997, the International Agency for Research on Cancer classified 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a group 1 human carcinogen, based largely on four highly exposed industrial cohorts that showed an excess of all cancers combined. In this study, we extended the follow-up period for the largest of these cohorts by 6 years and developed a job-exposure matrix., Methods: We did cohort mortality analyses involving 5132 chemical workers at 12 U.S. plants by use of life table techniques (U.S. population referent) and Cox regression (internal referent). We conducted exposure-response analyses for 69% of the cohort with adequate work history data and adequate plant data on TCDD contamination. All P values are two-sided., Results: The standardized mortality ratio (SMR) for all cancers combined was 1.13 (95% confidence interval = 1.02-1.25). We found statistically significant positive linear trends in SMRs with increasing exposure for all cancers combined and for lung cancer. The SMR for all cancers combined for the highest exposure group was 1.60 (95% confidence interval = 1.15-1.82). SMRs for heart disease showed a weak increasing trend with higher exposure (P = .14). Diabetes (any mention on the death certificate) showed a negative exposure-response trend. Internal analyses with Cox regression found statistically significant trends for cancer (15-year lag time) and heart disease (no lag)., Conclusions: Our analyses suggest that high TCDD exposure results in an excess of all cancers combined, without any marked specificity. However, excess cancer was limited to the highest exposed workers, with exposures that were likely to have been 100-1000 times higher than those experienced by the general population and similar to the TCDD levels used in animal studies.