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

Pharmacogenet Genomics. 2011 Oct;21(10):615-23. doi: 10.1097/FPC.0b013e3283493a57.


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=1.0×10(-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=2.0×10(-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Alleles
  • Epoxide Hydrolases / genetics
  • Genetic Association Studies
  • Glutamate-Cysteine Ligase / genetics*
  • Humans
  • Logistic Models
  • Male
  • Occupational Exposure
  • Oxidative Stress / genetics
  • Peroxidase / genetics
  • Pesticides / adverse effects*
  • Polymorphism, Single Nucleotide
  • Prostatic Neoplasms / genetics*
  • Risk Factors
  • Thioredoxin Reductase 2 / genetics
  • Xenobiotics / metabolism*


  • Pesticides
  • Xenobiotics
  • Peroxidase
  • TXNRD2 protein, human
  • Thioredoxin Reductase 2
  • Epoxide Hydrolases
  • EPHX1 protein, human
  • Glutamate-Cysteine Ligase