Introduction: Previous research has demonstrated increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, human biomonitoring studies indicate increased genetic damage with pesticide exposure. Given that the nucleotide excision repair (NER) pathway repairs a broad range of DNA damage, we evaluated interactions between pesticide use and 324 single nucleotide polymorphisms (SNPs) tagging 27 NER genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of white pesticide applicators in the Agricultural Health Study, a prospective cohort of pesticide applicators in Iowa and North Carolina.

Methods: We used likelihood ratio tests from logistic regression models to determine P-values for interactions between three-level pesticide variables (none/low/high) based on lifetime days of use weighted to an intensity score and SNPs (assuming a dominant model). We employed the False Discovery Rate (FDR) method to adjust for multiple comparisons.

Results: Of the seventeen interactions that met FDR<0.2, three also displayed a monotonic increase in prostate cancer risk with increasing pesticide use in one genotype group and no significant association in the other group. Men carrying the variant A allele at ERCC1 rs2298881 exhibited increased prostate cancer risk with high versus no fonofos use (Odds Ratio (OR): 2.98; 95% Confidence Interval (CI): 1.65–5.39; Pinteract=3.6×10–4; FDR-adjusted P=0.11). Men carrying the homozygous wild-type TT genotype at two correlated CDK7 SNPs, rs11744596 and rs2932778 (r2=1.0), exhibited increased prostate cancer risk with high versus no carbofuran use (OR: 2.01; 95% CI: 1.31–3.10 for rs11744596; Pinteract=7.2×10–4; FDR-adjusted P=0.09). In contrast, we did not observe associations with prostate cancer among men with other genotypes at these loci.

Conclusions: While requiring replication, our findings suggest a role for NER genetic variation in pesticide-associated prostate cancer risk.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B51.

Copyright © American Association for Cancer Research
2011