Background. Lipid metabolism processes have been implicated in prostate carcinogenesis. Since several pesticides are lipophilic or are metabolized via lipid-related mechanisms, they may interact with variants of genes in the lipid metabolism pathway. Methods. In a nested case-control study of 776 cases and 1444 controls from the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators, we examined the interactions between 39 pesticides (none, low, and high exposure) and 220 single nucleotide polymorphisms (SNPs) in 59 genes. The false discovery rate (FDR) was used to account for multiple comparisons. Results. We found 17 interactions that displayed a significant monotonic increase in prostate cancer risk with pesticide exposure in one genotype and no significant association in the other genotype. The most noteworthy association was for ALOXE3 rs3027208 and terbufos, such that men carrying the T allele who were low users had an OR of 1.86 (95% CI = 1.16–2.99) and high users an OR of 2.00 (95% CI = 1.28–3.15) compared to those with no use of terbufos, while men carrying the CC genotype did not exhibit a significant association. Conclusion. Genetic variation in lipid metabolism genes may modify pesticide associations with prostate cancer; however our results require replication. 1. Background Previous studies of prostate cancer have shown elevated rates in agricultural and pesticide manufacturing populations [1, 2]. In the Agricultural Health Study (AHS), a significant excess of prostate cancer was observed among private and commercial pesticide applicators compared to the general population [3, 4]. Also, use of pesticides, such as phorate [5], fonofos [6], butylate [7], and coumaphos [8], has been linked with an increased risk of prostate cancer among AHS participants with a family history of prostate cancer. We conducted a prostate cancer nested case-control study within the AHS to examine interactions between prespecified genetic pathways and pesticide exposure. Recent findings from this study have identified significant pesticide interactions for several genetic variants in the 8q24 region [9], xenobiotic metabolism pathway [10], and DNA repair pathways [11, 12]. These studies help elucidate exposure-effect associations by identifying potentially susceptible subgroups. This allows us to better understand potential carcinogenic hazards and furthers public health research on the human health effects of pesticides. In this analysis, we evaluated single nucleotide polymorphisms (SNPs) in genes related to lipid metabolism since
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