Pesticide exposure and inherited variants in vitamin D pathway genes in relation to prostate cancer
Menée sur 776 patients atteints d'un cancer de la prostate et sur 1 444 témoins, cette étude évalue l'association entre 41 pesticides, 152 polymorphismes à simple nucléotide de 9 gènes impliqués dans la voie de la vitamine D et le risque de développer la maladie
Background : Vitamin D and its metabolites are believed to 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. We hypothesize that certain pesticides may be linked to prostate cancer via an interaction with vitamin D genetic variants. 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 Caucasian 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 (FDR) to account for multiple comparisons. Results : Five significant interactions (P<0.01) displayed a monotonic increase in prostate cancer risk with individual pesticide use in one genotype and no association in the other. These interactions involved parathion and terbufos use and three vitamin D genes (VDR, RXRB and GC). The exposure-response pattern among participants with increasing parathion use with the homozygous CC genotype for GC rs7041 compared to unexposed participants was noteworthy (low versus no exposure: odds ratio (OR)=2.58, 95% confidence interval (CI)=1.07-6.25; high versus no exposure: OR=3.09, 95%CI=1.10-8.68; P-interaction=3.8x10-3). Conclusions : In this study, genetic variations in vitamin D pathway genes, particularly GC rs7041, a SNP previously linked to lower circulating vitamin D levels modified pesticide associations with prostate cancer risk. Impact : Because our study is the first to examine this relationship, additional studies are needed to rule out chance findings.