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.
Since base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single nucleotide 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.
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.
The interaction between fonofos and rs1983132 in NEIL3, which encodes a glycosylase that can initiate BER, was the most significant overall (pinteract=9.3x10-6; 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 and 95% confidence intervals for low and high use versus no use of 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 FDR< 0.2.
Our significant fonofos finding is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. While requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.
Written by:
Barry KH, Koutros S, Berndt SI, Andreotti G, Hoppin JA, Sandler DP, Burdette LA, Yeager M, Beane Freeman LE, Lubin JH, Ma X, Zheng T, Alavanja MC. Are you the author?
Reference: Environ Health Perspect. 2011 Aug 2. Epub ahead of print.
doi: 10.1289/ehp.1103454
PubMed Abstract
PMID: 21810555
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