Background: Several investigations assessed the association of Vitamin D receptor (VDR) SNPs with cancer risk. Less is known about the implications of other Vitamin D pathway SNPs on cancer risk. Methods: In a population-based cohort study of 9,949 German older adults, we used Cox regression to assess the association of 6 SNPs in the VDR, Vitamin D-binding protein (GC), 7-dehydrocholesterol reductase (DHCR7), Vitamin D 25- hydroxylase (CYP2R1), and Vitamin D 24-hydroxylase (CYP24A1) genes with total and site-specific cancer incidence endpoints. Results: Overall, no association of SNPs with cancer incidence endpoints was observed, except for a genotype score based on SNPs associated with lower 25(OH)D, which was associated with higher lung cancer risk [HR, 1.20; 95% confidence intervals (CI), 1.03-1.39], although this was no longer significant after correcting for multiple testing. Conclusions: Our data provide little to no evidence of a major influence of Vitamin D genetic predisposition on cancer risks. Impact: Large-scale genetic epidemiology consortia and metaanalysis of smaller published studies are needed to verify a potential modest influence of genetic variation in the association of Vitamin D with the risk of cancer.
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