A weight-of-evidence review of colorectal cancer in pesticide applicators: the agricultural health study and other epidemiologic studies

To systematically evaluate epidemiologic studies on pesticides and colon cancer and rectal cancer in agricultural pesticide applicator populations using a transparent "weight-of-evidence" (WOE) methodological approach. Twenty-nine (29) publications from the Agricultural Health Study (AHS) and 13 additional epidemiologic studies were identified that reported data for pesticide applicators and/or specific pesticide compounds and colorectal, colon, or rectal cancer. The AHS evaluated pesticide applicators as well as dose-response associations for specific pesticide compounds, whereas the large majority of non-AHS evaluated applicators but did not analyze specific compounds or dose-response trends. This WOE assessment of 153 different pesticide-outcome pairs emphasized several key evidentiary features: existence of statistically significant relative risks, magnitude of observed associations, results from the most reliable exposure assessments, and evidence of convincing dose-response relationships (i.e., those monotonically increasing, with statistically significant trend tests). Occupation as a pesticide applicator or pesticide application as a farming-related function was not associated with increasing the risk of colon or rectal cancer. Deficits of colon or rectal cancer were observed across most studies of pesticide applicators. After applying the WOE methodology to the epidemiologic studies of specific pesticide compounds and colon or rectal cancer, a number of pesticide-outcome pairs were identified and evaluated further based on positive statistical associations. Of these, only two-aldicarb and colon cancer and imazethapyr and proximal colon cancer-appears to warrant further discussion regarding a possible causal relationship, although the epidemiologic data are limited. For the remainder, a lack of a clear dose-response trend, inconsistencies in associations between exposure metrics and comparison groups, imprecise associations, variable participation rates for analyses of specific compounds, and the reliance upon data from one study (the AHS) limit interpretation regarding risk. The available epidemiologic evidence does not support a causal relationship between occupation as a pesticide applicator or specific pesticide exposures and colon or rectal cancer.