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Title: Xenobiotic-metabolizing gene variants, pesticide use, and the risk of prostate cancer.
Authors: Koutros S,  Andreotti G,  Berndt SI,  Hughes Barry K,  Lubin JH,  Hoppin JA,  Kamel F,  Sandler DP,  Burdette LA,  Yuenger J,  Yeager M,  Alavanja MC,  Freeman LE
Journal: Pharmacogenet Genomics
Date: 2011 Oct
Branches: BB, CGR, OEEB
PubMed ID: 21716162
PMC ID: PMC3172373
Abstract: BACKGROUND: To 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. OBJECTIVE: [corrected] We 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. METHODS: We 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. RESULTS: A positive monotonic interaction was observed between petroleum oil/petroleum distillate use and rs1883633 in the oxidative stress gene glutamate cysteine ligase (GCLC; P interaction=1.010(-4)); men carrying at least one variant allele (minor allele) experienced an increased prostate cancer risk (OR=3.7, 95% CI: 1.9-7.3). 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% CI: 1.1-3.2, P interaction=0.01; OR=2.1, 95% CI: 1.1-4.0, P interaction=0.01), or terbufos (OR=3.0, 95% CI: 1.5-6.0, P interaction=2.010(-3)) 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. CONCLUSION: We 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.