Xenobiotic-metabolizing gene variants, pesticide use, and the risk of prostate cancer

BACKGROUNDTo explore associations with prostate cancer and farming, it is important to investigate the relationship between pesticide use and single nucleotide polymorphisms (SNPs) in xenobiotic metabolic enzyme (XME) genes. OBECTIVEWe evaluated pesticide–SNP interactions between 45 pesticides and 1913 XME SNPs with respect to prostrate cancer among 776 cases and 1444 controls in the Agricultural Health Study. METHODSWe used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP–pesticide interactions were calculated using a likelihood ratio test. RESULTSA positive monotonic interaction was observed between petroleum oil/petroleum distillate use and rs1883633 in the oxidative stress gene glutamate cysteine ligase (GCLC; P interaction=1.0×10); men carrying at least one variant allele (minor allele) experienced an increased prostate cancer risk (OR=3.7, 95% CI1.9–7.3). Among men carrying the variant allele for thioredoxin reductase 2 (TXNRD2) rs4485648, microsomal epoxide hydrolase 1 (EPHX1) rs17309872, or myeloperoxidase (MPO) rs11079344, an increased prostate cancer risk was observed with high, compared with no, petroleum oil/petroleum distillate (OR=1.9, 95% CI1.1–3.2, P interaction=0.01; OR=2.1, 95% CI1.1–4.0, P interaction=0.01), or terbufos (OR=3.0, 95% CI1.5–6.0, P interaction=2.0×10) use, respectively. No interactions were deemed noteworthy at the false discovery rate=0.20 level; the number of observed interactions in XMEs was comparable with the number expected by chance alone. CONCLUSIONWe observed several pesticide–SNP interactions in oxidative stress and phase I/II enzyme genes and risk of prostate cancer. Additional work is needed to explain the joint contribution of genetic variation in XMEs, pesticide use, and prostate cancer risk.