Carbaryl use and incident cancer in the Agricultural Health Study: an updated analysis

Carbaryl is a common carbamate insecticide in the United States (USA). Previous epidemiologic investigations, including within the Agricultural Health Study (AHS), have suggested potential associations between carbaryl use and cancer risk. The AHS is a prospective cohort study of licensed pesticide applicators in North Carolina (NC) and Iowa (IA), USA. Information on lifetime pesticide use was reported at enrollment (1993-1997) and follow-up (1999-2005). We evaluated cancer risks associated with ever- and intensity-weighted lifetime days (IWLD) of carbaryl use. Among 52,625 applicators, 8713 incident cancer cases were identified from linkages with state cancer registries through 2014 (NC) or 2017 (IA). We used Poisson regression to estimate rate ratios (RR) and 95 % confidence intervals (CI), controlling for confounders, and evaluated lagged exposures. Approximately 51 % of applicators reported using carbaryl. Increasing IWLD of carbaryl use was associated with increased stomach cancer risk (third tertile vs. never use; RR_T3 = 2.07, 95 % CI: 1.05-4.07, p-trend = 0.02), persisting when exposure was lagged by 5-years (RR_T3 = 2.20, 95 % CI: 1.12-4.33). We noted elevated risks of esophageal (RR = 1.52, 95 % CI: 1.01-2.27) and tongue (RR = 1.91, 95 % CI: 0.95-3.81) cancers with ever-use. There was an increased risk of aggressive prostate cancer when carbaryl exposure was lagged by 30 years (RR_lag30Q4 = 1.56, 95 % CI: 1.18-2.08, p-trend = 0.002). This is the largest and most comprehensive prospective evaluation of carbaryl and cancer risk to date. We provide novel evidence of associations between carbaryl exposure and specific cancers. There is a need for additional studies to confirm these findings and to elucidate the biological mechanisms underlying the observed associations.