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Background:

Agricultural work and occupational pesticide use have been associated with increased risk of renal cell carcinoma (RCC), the most common form of kidney cancer. However, few prospective studies have investigated links to specific pesticides.

Objective:

We evaluated the lifetime use of individual pesticides and the incidence of RCC.

Methods:

We evaluated the associations between intensity-weighted lifetime days (IWDs) of 38 pesticides and incident RCC in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Among 55,873 applicators, 308 cases were diagnosed between enrollment (1993–1997) and the end of follow-up (2014–2015). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounding factors, with lagged and unlagged pesticide exposures.

Results:

There was a statistically significant increased risk of RCC among the highest users of 2,4,5-T compared with never users [unlagged ${\text{RR}}_{\text{IWD Tertile\hspace{0.17em}}3}=2.92$ (95% CI: 1.65, 5.17; $p_{\text{trend}}=0.001$)], with similar risk estimates for lagged exposure [20-y lag ${\text{RR}}_{\text{IWD Tertile\hspace{0.17em}}3}=3.37$ (95% CI: 1.83, 6.22; $p_{\text{trend}}=0.001$)]. In 20-y lagged analyses, we also found exposure–response associations with chlorpyrifos [${\text{RR}}_{\text{IWD Quartile\hspace{0.17em}}4}=1.68$ (95% CI: 1.05, 2.70; $p_{\text{trend}}=0.01$)], chlordane [${\text{RR}}_{\text{IWD Tertile\hspace{0.17em}}3}=2.06$ (95% CI: 1.10, 3.87; $p_{\text{trend}}=0.02$)], atrazine [${\text{RR}}_{\text{IWD Quartile\hspace{0.17em}}4}=1.43$ (95% CI: 1.00, 2.03; $p_{\text{trend}}=0.02$)], cyanazine [${\text{RR}}_{\text{IWD Quartile\hspace{0.17em}}4}=1.61$ (95% CI: 1.03, 2.50; $p_{\text{trend}}=0.02$)], and paraquat [${\text{RR}}_{\text{IWD}>\text{Median}}=1.95$ (95% CI: 1.03, 3.70; $p_{\text{trend}}=0.04$)].

Conclusions:

This is, to our knowledge, the first prospective study to evaluate RCC risk in relation to various pesticides. We found evidence of associations with RCC for four herbicides (2,4,5-T, atrazine, cyanazine, and paraquat) and two insecticides (chlorpyrifos and chlordane). Our findings provide insights into specific chemicals that may influence RCC risk among pesticide applicators. Confirmation of these findings and investigations of the biologic plausibility and potential mechanisms underlying the observed associations are warranted. https://doi.org/10.1289/EHP6334