Cancer, heart disease, and diabetes in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

Background: In 1997, the International Agency for Research on Cancer classi fied 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a group 1 human carcinog en, based largely on four highly exposed industrial cohorts that showed an excess of all cancers combined. In this study, we extended the follow-up pe riod for the largest of these cohorts By 6 years and developed a job-exposu re matrix. Methods: We did cohort mortality analyses involving 5132 chemica l workers at 12 U.S. plants by use of life table techniques (U.S. populatio n referent) and Cox regression (internal referent). We conducted exposure-r esponse analyses for 69% of the cohort with adequate work history data and adequate plant data on TCDD contamination, All P values are two-sided. Resu lts: The standardized mortality ratio (SMR) for all cancers combined was 1. 13 (95% confidence interval = 1.02-1.25). We found statistically significan t positive linear trends in SMRs with increasing exposure for all cancers c ombined and for lung cancer. The SMR for all cancers combined for the highe st 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 exposur e-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, ex cess cancer was limited to the highest exposed workers, with exposures that were likely to have been 100-1000 times higher than those experienced by t he general population and similar to the TCDD levels used in animal studies .