Abstract
To inform risk assessment and regulatory decision-making, the relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and prostate cancer requires clarification. This article systematically and critically reviews the epidemiologic evidence on the association between exposure to TCDD or Agent Orange, a TCDD-contaminated herbicide used during the Vietnam War, and prostate cancer risk. Articles evaluated include 11 studies of three cohorts, four case–control or cross-sectional studies, and three case-only studies of military veterans with information on estimated Agent Orange or TCDD exposure; 13 studies of seven cohorts, one case–control study, and eight proportionate morbidity or mortality studies of Vietnam veterans without information on Agent Orange exposure; 11 cohort studies of workers with occupational exposure to TCDD; and two studies of one community cohort with environmental exposure to TCDD. The most informative studies, including those of Vietnam veterans involved in Agent Orange spraying or other handling, herbicide manufacturing or spraying workers with occupational TCDD exposure, and community members exposed to TCDD through an industrial accident, consistently reported no significant increase in prostate cancer incidence or mortality. Only some potentially confounded studies of Vietnam veterans compared with the general population, studies with unreliable estimates of Agent Orange exposure, and analyses of selected subgroups of Vietnam veterans reported positive associations. Overall, epidemiologic research offers no consistent or convincing evidence of a causal relationship between exposure to Agent Orange or TCDD and prostate cancer. More accurate exposure assessment is needed in large epidemiologic studies to rule out a causal association more conclusively.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-014-9931-2) contains supplementary material, which is available to authorized users.
Highlights
Prostate cancer is the most common non-skin malignancy in U.S men and the second most common cancer in men globally [1]
Results regarding the association between TCDD exposure and risk of prostate cancer were presented from only three epidemiologic studies reviewed in the earlier International Agency for Research on Cancer (IARC) evaluation in 1997 [6]; none of these detected a significant increase in prostate cancer incidence or mortality among workers potentially exposed to TCDD [8–10]
One of these reports [15] cited any results for prostate cancer, noting that this outcome was not increased above expectation in a pooled international cohort of workers exposed to phenoxy herbicides and chlorophenols contaminated with TCDD [17]
Summary
Prostate cancer is the most common non-skin malignancy in U.S men and the second most common cancer in men globally [1]. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been proposed as a possible cause of prostate cancer [5]. In 1997 and 2012, the International Agency for Research on Cancer (IARC) classified TCDD as an established human carcinogen (IARC group 1) [6, 7]. 100 missing TCDD 17 with nonquantifiable TCDD 1 reported cancer not verified by medical record 11 with cancer before service in Southeast Asia 1,493 comparison subjects compliant at any examination 140 missing TCDD 50 with nonquantifiable TCDD 25 with dioxin [10 ppt 3 with cancer before service in Southeast Asia ORs adjusted for birth year, military occupation, race, percent body fat at time of dioxin blod draw, lifetime cigarette smoking, lifetime alcohol consumption, and exposure to asbestos, ionizing radiation, industrial chemicals, herbicides, insecticides, and degreasing chemicals Author Study subjects.
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