iants on Chromosome 8q24 and Prostate Cancer

Downlo ome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In ricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased te cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, aluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors ted odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, ticides, and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, 382, and prostate cancer increased significantly (P < 0.05) with exposure to the organophosphate insecfonofos, after correction for multiple testing, with per allele ORnonexposed of 1.17 (95% CI, 0.93–1.48), per ORlow of 1.30 (95% CI, 0.75–2.27), and per allele ORhigh of 4.46 (95% CI, 2.17–9.17; P-interaction = 0.002, ed P-interaction = 0.02). A similar effect modification was observed for three other organophosphate indes (coumaphos, terbufos, and phorate) and one pyrethroid insecticide (permethrin). Among ever users of s, subjects with three or four risk alleles at rs7837328 and rs4242382 had approximately three times the risk state cancer (OR, 3.14; 95% CI, 1.41–7.00) compared with subjects who had zero risk alleles and never used s. We observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of te cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the prosta biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk. Cancer Res; 70(22); 9224–33. ©2010 AACR.