Data from Genetic Variation in the Vitamin D Receptor (<i>VDR</i>) and the Vitamin D–Binding Protein (<i>GC</i>) and Risk for Colorectal Cancer: Results from the Colon Cancer Family Registry

Abstract

<div>Abstract<p>Epidemiologic evidence supports a role for vitamin D in colorectal cancer (CRC) risk. Variants in vitamin D–related genes might modify the association between vitamin D levels and CRC risk. In this analysis, we did a comprehensive evaluation of common variants in the vitamin D receptor (<i>VDR</i>) and the vitamin D–binding protein (<i>GC</i>; group-specific component) genes using a population-based case–unaffected sibling control design that included 1,750 sibships recruited into the Colon Cancer Family Registry. We also evaluated whether any associations differed by calcium supplement use, family history of CRC, or tumor characteristics. Heterogeneity by calcium and vitamin D intake was evaluated for a subset of 585 cases and 837 sibling controls who completed a detailed food frequency questionnaire. Age- and sex-adjusted associations were estimated using conditional logistic regression. Overall, we did not find evidence for an association between any single-nucleotide polymorphism (SNP) in <i>VDR</i> or <i>GC</i> and risk for CRC (range of unadjusted <i>P</i> values 0.01-0.98 for <i>VDR</i> and 0.07-0.95 for <i>GC</i>). None of these associations was significant after adjustment for multiple comparisons. We also found no evidence that calcium or vitamin D intake (food and supplement) from the food frequency questionnaire modified the association estimates between <i>VDR</i> and <i>GC</i> SNPs and CRC. We did observe associations between SNPs in <i>GC</i> and microsatellite unstable CRC, although these results should be confirmed in additional studies. Overall, our results do not provide evidence for a role of common genetic variants in <i>VDR</i> or <i>GC</i> in susceptibility to CRC. Cancer Epidemiol Biomarkers Prev; 19(2); 525–36</p></div>