Prostate cancer in relation to pesticide use and inherited variants in vitamin D pathway genes

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NCI	EPID-11

Authors

• S Karami
• G Andreotti
• S Koutros
• KH Barry
• S Han
• LE Moore
• A Blair
• JA Hoppin
• DP Sandler
• JH Lubin
• LA Burdette
• J Yuenger
• M Yeager
• LE Beane Freeman
• MCR Alavanja

Abstract

Introduction-Vitamin D may impede carcinogenesis by stimulating cell differentiation, inhibiting cell proliferation and inducing apoptosis. Certain pesticides have been shown to deregulate vitamin D’s anti-carcinogenic properties. Methods-We evaluated interactions between 41 pesticides and 152 single nucleotide polymorphisms (SNPs) in nine vitamin D pathway genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of pesticide applicators within the Agricultural Health Study. We assessed interaction P-values using likelihood ratio tests from unconditional logistic regression and a False Discovery Rate to account for multiple comparisons. Results-Five significant interactions, robust to multiple comparison adjustment, displayed a monotonic increase in cancer risk with pesticide use in one genotype and no association in the other. These interactions involved parathion and terbufos and three vitamin D genes (VDR, RXRB, GC). Exposure-response patterns among subjects with increasing parathion use with the GC rs7041 homozygous CC genotype compared to unexposed subjects was noteworthy (low vs. no exposure: OR=2.58, 95% confidence interval (CI)=1.07-6.25; high vs. no exposure: OR=3.09, 95%CI=1.10-8.68; P-interaction=3.8x10-3). Discussion-Genetic variations in vitamin D pathway genes, particularly GC rs7041, a SNP linked to lower circulating vitamin D levels may modify pesticide associations with prostate cancer risk. Additional studies are needed to replicate findings.

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