The authors reviewed the epidemiologic studies on exposure to
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD) and
cancer risk, published since the last full-scale review made by the International Agency for Research on
Cancer Monographs program in 1997. The update of a cohort of US
herbicide producers generated negative results overall; the internal analysis provided evidence of an increased "all-
cancer" risk in the highest exposure category, with a statistically significant exposure-response association in some of the many analyses performed. The update of a similar Dutch cohort did not confirm the previously observed association with
TCDD exposure. The updated surveillance of the Seveso population provided evidence of increased all-
cancer mortality 15-20 years after exposure among those living in the most contaminated area but might also reflect random variation, as overall excesses in the most recent follow-up were not observed. Corresponding data on
cancer incidence offer little support to the mortality results. Updated results from cohort studies of Vietnam veterans potentially exposed to
TCDD did not consistently suggest an increased risk of
cancer. Results of additional, smaller studies of other occupational groups potentially exposed to
TCDD, and of community-based case-control studies, did not provide consistent evidence of an increased
cancer risk. In conclusion, recent epidemiological evidence falls far short of conclusively demonstrating a causal link between
TCDD exposure and
cancer risk in humans. The emphasis on results for overall
cancer risk-rather than risk for specific
neoplasms-is not justified on epidemiologic grounds and is not a reason for ignoring the weaknesses of the available evidence.