Vitamin D receptor start codon polymorphism and colorectal cancer risk: effect modification by dietary calcium and fat in Singapore Chinese

Vitamin D has been implicated as a protective agent against colorectal cancer. We hypothesized that a functional start codon polymorphism in the vitamin D receptor (VDR) influences the risk of colorectal carcinoma. We conducted a case-control study nested within a large cohort of Singapore Chinese. VDR genotypes, determined by FokI restriction endonuclease digestion of PCR-amplified DNA, were performed on 217 colorectal cancer cases and 890 controls. We found that compared with individuals carrying the FF genotype, those with Ff genotype had a 51% increase in risk of colorectal cancer and those with the ff genotype, an 84% increase in risk (P for trend = 0.01). The effect of the VDR genotype on risk appeared to be modified by both dietary calcium and fat. Among those with either low calcium or low fat intake (below the median values in controls), the risk for colorectal cancer increased in a gene-dose-dependent manner such that individuals possessing the ff genotype displayed an approximately 2.5-fold increased risk that was statistically significant. There was little evidence of a VDR genotype-colorectal cancer association among subjects with higher than median values of either dietary fat or calcium.