Abstract A109: A prospective study of vitamin D receptor polymorphisms, interaction with vitamin D status, and colorectal cancer risk in men

Abstract

Abstract A109 Growing evidence suggests an elevated risk of colorectal cancer among individuals with low levels of vitamin D, the biological actions of which is mediated by the vitamin D receptor (VDR). We examined the prospective associations between three VDR single nucleotide polymorphisms (SNPs) (BsmI (bb, bB/BB), FokI (FF, Ff/ff), and Cdx2 (G>A)) and colorectal cancer risk and their interactions with plasma vitamin D status in a nested case-control study among men in the Physicians’ Health Study. A total of 249 incident colorectal cancer cases were identified through 2000 among men who provided blood specimens in 1982-1984 and individually matched to controls by age and smoking. We used conditional logistic regression to calculate the relative risk (RR) and 95% confidence interval (95% CI). We found that men with the VDR Cdx2 variant A allele tended to have a lower risk of developing colorectal cancer compared to men with the homozygous GG genotype (RR=0.71; 95% CI = 0.50-1.02; P = 0.06). Moreover, the lower risk of colorectal cancer associated with the VDR Cdx2 A genotype was mainly confined to men with low vitamin D status (plasma 25(OH)D below median level; RR = 0.45; 95% CI = 0.24-0.84; P = 0.03) but not among men with vitamin D levels above the median (P for interaction = 0.04). We found no statistically significant associations for the other two VDR SNPs, FokI or BsmI, or statistically significant interactions between plasma 25(OH)D levels and these two SNPs. Our prospective data suggest the hypothesis that the functional polymorphic Cdx2 A allele variation in the VDR gene, which is linked to a higher transcriptional activity of the VDR, may be protective against colorectal cancer development when vitamin D status is low. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A109.