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

  1. Author:
    Koutros, S.
    Andreotti, G.
    Berndt, S. I.
    Barry, K. H.
    Lubin, J. H.
    Hoppin, J. A.
    Kamel, F.
    Sandler, D. P.
    Burdette, L. A.
    Yuenger, J.
    Yeager, M.
    Alavanja, M. C. R.
    Freeman, L. E. B.

  2. Author Address

    [Koutros, S] NCI, Div Canc Epidemiol & Genet, US Dept HHS, Occupat & Environm Epidemiol Branch,NIH, Rockville, MD 20852 USA. [Burdette, LA; Yuenger, J; Yeager, M] NCI, Core Genotyping Facil, Adv Technol Program, Frederick, MD 21701 USA. [Hoppin, JA; Kamel, F; Sandler, DP] NIEHS, US Dept HHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.;Koutros, S (reprint author), NCI, Div Canc Epidemiol & Genet, US Dept HHS, Occupat & Environm Epidemiol Branch,NIH, 6120 Execut Blvd,EPS 8115,MSC 7240, Rockville, MD 20852 USA;KoutrosS@mail.nih.gov
    1. Year: 2011
    2. Date: Oct
  2. Journal: Pharmacogenetics and Genomics
    1. 21
    2. 10
    3. Pages: 615-623
  4. Type of Article: Article
  5. ISSN: 1744-6872
  1. 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. Obective 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 X 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 X 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. Pharmacogenetics and Genomics 21: 615-623 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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  2. DOI: 10.1097/FPC.0b013e3283493a57
  3. View record in Web of Science®
  4. WOS: 000294808900001

Library Notes

  1. Fiscal Year: FY2011-2012
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