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Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk

  1. Author:
    Barry, K. H.
    Koutros, S.
    Bemdt, S. I.
    Andreotti, G.
    Hoppin, J. A.
    Sandler, D. P.
    Burdette, L. A.
    Yeager, M.
    Freeman, L. E. B.
    Lubin, J. H.
    Ma, X. M.
    Zheng, T. Z.
    Alavanja, M. C. R.

  2. Author Address

    [Barry, Kathryn Hughes; Koutros, Stella; Bemdt, Sonja I.; Andreotti, Gabriella; Yeager, Meredith; Freeman, Laura E. Beane; Lubin, Jay H.; Alavanja, Michael C. R.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Barry, Kathryn Hughes; Ma, Xiaomei; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Hoppin, Jane A.; Sandler, Dale P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Burdette, Laurie A.; Yeager, Meredith] NCI, Core Genotyping Facil, Frederick, MD 21701 USA.;Barry, KH (reprint author), Natl Canc Inst, 6120 Executive Blvd,EPS 8111,MSC 7240, Bethesda, MD 20892 USA;barrykh@mail.nih.gov
    1. Year: 2011
    2. Date: Dec
  2. Journal: Environmental Health Perspectives
    1. 119
    2. 12
    3. Pages: 1726-1732
  4. Type of Article: Article
  5. ISSN: 0091-6765
  1. Abstract:

    BACKGROUND: Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage. OBJECTIVES: Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single-nudeotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of white Agricultural Health Study (AHS) pesticide applicators. METHODS: We used likelihood ratio tests from logistic regression models to determine p-values for interactions between three-level pesticide exposure variables (none/low/high) and SNPs (assuming a dominant model), and the false discovery rate (FDR) multiple comparison adjustment approach. RESULTS: The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)] which encodes a glycosylase that can initiate BER, was the most significant overall [interaction p-value (p(interact)) = 9.3 x 10(-6); FDR-adjusted p-value = 0.01]. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for rs1983132 [odds ratios (95% confidence intervals) for low and high use compared with no use were 1.65 (0.91, 3.01) and 3.25 (1.78, 5.92), respectively], whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. Carbofuran and S-ethyl dipropylthiocarbamate (EPTC) interacted similarly with rs1983132; however, these interactions did not meet an FDR < 0.2. CONCLUSIONS: Our significant finding regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.

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External Sources

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  2. DOI: 10.1289/ehp.1103454
  3. View record in Web of Science®
  4. WOS: 000297711200025

Library Notes

  1. Fiscal Year: FY2011-2012
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