TCDD and cancer: A critical review of epidemiologic studies

Abstract

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.

Keywords::

• Cancer
• dioxin
• epidemiology
• TCDD

Acknowledgments

The authors wish to acknowledge the valuable assistance of Ms. Brooke Nichols, MS, in searching and obtaining copies of papers considered for review, verifying references and data presented in figures and tables, and editing of the manuscript.

Declaration of interest

This review was sponsored by an unrestricted grant from the Research Foundation for Health and Environmental Effects (RFHEE), a tax-exempt organization established by the Chlorine Chemistry Division of the American Chemistry Council (ACC), Washington, DC. All authors contributed to the review as independent scientists and were compensated by the grant.

The content of the paper is the sole responsibility of the authors and does not necessarily represent the views or opinions of RFHEE, or any of the employers of the authors. As the sponsor, RFHEE did not influence the methods and materials used by the authors in conducting their independent review and synthesis of the epidemiological literature, or the interpretation of the results.

Dr. K. Mundt was invited by RFHEE to present the findings of this review at a public meeting of the US Environmental Protection Agency’s Science Advisory Board (SAB) Dioxin Review Panel, Wednesday, October 27, 2010, in Washington, DC, and ENVIRON was reimbursed for costs associated with Dr. Mundt’s attendance at the SAB Dioxin Review Panel meeting.

Notes

¹Additional papers published shortly after the 1997 IARC Monograph on the 4-plant German cohort (Becher et al., 1998; Flesch-Janys et al., 1998), and the Danish cohort (Lynge et al., 1998) were based on the same data included in the multicenter study (Kogevinas et al., 1997), and therefore are not reviewed in detail here.

²An additional report of mortality among the workers in this factory has been published (Bodner et al., 2003).

³Additional reports based on follow-up of cancer incidence to 1991 and mortality to 1996 (Bertazzi et al., 2001; Pesatori et al., 2003) are not reviewed in detail.

⁴An additional report based on cancer mortality to 1993 (Michalek et al., 1998) is not reviewed in detail.

⁵These results were derived by summing up observed and expected deaths in White and non-White veterans reported in the original publication.