Plasma dioxin levels and cause-specific mortality in an occupational cohort of workers exposed to chlorophenoxy herbicides, chlorophenols and contaminants
该研究利用荷兰除草剂队列中187名工人的血浆二恶英水平，建立预测模型，发现二恶英暴露与全因、缺血性心脏病和非霍奇金淋巴瘤死亡率相关，但未解释此前报告的癌症风险增加。
BACKGROUND: We recently reported increased risks for all cancers and urinary cancers in workers exposed to chlorophenoxy herbicides using data from the Dutch herbicide cohort study. These risks could not be linked to the qualitative exposure proxies available. Here, we re-investigate exposure-response relationships using a (semi)quantitative measure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. METHODS: Plasma TCDD levels of 187 workers were used to develop a predictive model for TCDD exposure. Cox proportional hazards model was used to investigate associations between time-varying TCDD exposure and cause-specific mortality. Sensitivity analyses were performed to assess the impact of key assumptions in exposure assessment. RESULTS: Predicted TCDD levels were associated with mortality from all causes (HR 1.08; 95% CI 1.03 to 1.13), ischaemic heart disease (IHD; HR 1.19; 95% CI 1.08 to 1.32) and non-Hodgkin's lymphoma (NHL; HR 1.36; 95% CI 1.06 to 1.74). No relationships were found between TCDD exposure and mortality from all cancers, respiratory or urinary cancers, which were previously linked to qualitative proxies of TCDD exposure in this cohort. Sensitivity analyses showed that results were relatively robust to slight changes in exposure estimation. CONCLUSIONS: Modelled TCDD exposure does not explain the previously reported increased risks for cancer mortality in this cohort except for a possible association with NHL. A small increase in ischaemic heart disease was observed, however we cannot exclude that this finding was due to residual confounding. Although risk estimates for some of the rarer outcomes were still rather imprecise, we do not expect more precise estimates from longer follow-up of this cohort due to the long time-span since last exposure to TCDD.