Significant issues raised by meta-analyses of cancer mortality and dioxin exposure

Consistent with results from an earlier U.S. Environmental Protection Agency meta-analysis of three occupational cohorts, Crump et al. [Environ Health Perspect 111:681-687 (2003)] recently concluded that "dioxin TEQ [toxic equivalent] exposures within roughly 3-fold of current background levels may be carcinogenic" to humans. In contrast, my meta-analysis using an intercept-only model implied zero additional human cancer deaths from all exposures to dioxin-like compounds, including those arising via dietary intake. How can different investigators reach such markedly different conclusions from similar analyses of essentially the same data? The answer lies in different selections for a dose metric, different assumptions regarding the elimination half-life for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans, different assumptions regarding the importance of the most recent 15 years of exposure, and extrapolations from potential effects of TCDD exposure to potential effects of TEQ exposures. Resolution of the ongoing debate regarding the potential human carcinogenicity of dioxin will require detailed information on exposure to TCDD and on direct-acting carcinogens in the workplace, as well as a dose-response model that adequately reflects TCDD's characteristics as a promoter.