Genetic variation in DNA repair genes, pesticide exposure, and prostate cancer risk

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NCI	EPID-2

* FARE Award Winner

Authors

• KH Barry
• S Koutros
• SI Berndt
• G Andreotti
• JA Hoppin
• DP Sandler
• LA Burdette
• M Yeager
• LE Beane Freeman
• JH Lubin
• X Ma
• T Zheng
• MC Alavanja

Abstract

Various pesticide exposures have been associated with increased DNA damage, suggesting that this mechanism might contribute to pesticide-associated cancer risk. We evaluated interactions between pesticide exposure and genetic variation in 31 base excision repair (BER) and 27 nucleotide excision repair (NER) pathway genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of white Agricultural Health Study pesticide applicators. We estimated interaction P-values using likelihood ratio tests from logistic regression models. Fonofos was associated with increased prostate cancer risk among men carrying CT/TT genotypes for rs1983132 in the BER gene NEIL3 (Odds Ratio (OR) for high versus no fonofos use=3.25; 95% Confidence Interval (CI): 1.78-5.92; Pinteract=9.3x10-6; False Discovery Rate (FDR)-adjusted P=0.01) or CA/AA genotypes for rs2298881 in the NER gene ERCC1 (OR=2.98; 95% CI: 1.65-5.39; Pinteract=3.6x10-4; FDR-adjusted P=0.11). Carbofuran was associated with increased risk among men carrying the TT genotype for two highly correlated polymorphisms (r2=1.0) tagging the NER gene CDK7, rs11744596 and rs2932778 (OR=2.01; 95% CI: 1.31-3.10 for rs11744596; Pinteract=7.2x10-4; FDR-adjusted P=0.09). In contrast, associations were null among men with other genotypes. Our findings suggest that BER and NER genetic variation might influence susceptibility to prostate cancer among those exposed to certain pesticides.

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