Objectives Pesticides have been associated with prostate cancer risk, but few studies have evaluated specific pesticides and studies have not explored differences by subtype to identify important risk for the more lethal, aggressive, form of prostate cancer. Therefore, we studied the risk of prostate cancer associated with specific pesticides among 1,962 incident cases, including 919 cases of aggressive prostate cancer (distant Stage or poorly differentiated or Gleason ≥7 or fatal prostate cancer) diagnosed between 1993 and 2007 from 54,412 men of the Agricultural Health Study (AHS) cohort.

Methods Poisson regression analysis was used to calculate rate ratios (RR) and 95% confidence intervals (95% CI) for lifetime use of 48 pesticides and prostate cancer incidence.

Results There was no overall association between any specific pesticide and prostate cancer risk. However, three organophosphate insecticides were significantly associated with aggressive prostate cancer: fonofos (RR for the highest quartile of exposure (Q4) versus nonexposed = 1.63, 95% CI: 1.22–2.17; p-trend <0.001), malathion (RR for Q4 versus nonexposed = 1.43, 95% CI: 1.08–1.88; p-trend = 0.04), and terbufos (RR for Q4 versus nonexposed = 1.29, 95% CI: 1.02–1.64; p-trend = 0.03). The organochlorine insecticide aldrin was also significantly associated with risk of aggressive prostate cancer with a RR for Q4 versus nonexposed = 1.49, 95% CI: 1.03–2.18; p-trend = 0.02.

Conclusions Four insecticides were observed to increase the risk of aggressive prostate cancer in the AHS. Advantages of this analysis over previous analyses include a large number of prostate cancer cases and detailed information on lifetime use of specific pesticides. This is the first time specific pesticides have been studied and implicated as risk factors for aggressive prostate cancer and may suggest that pesticides play a role in prostate cancer progression rather than at the earlier initiation stage of transformation.