Associations between Vitamin D Receptor (VDR) Gene Polymorphisms and Colorectal Cancer Risk and Effect Modifications of Dietary Calcium and Vitamin D in a JapanesePopulation

Much interest has been drawn to possible associations between vitamin D receptor (VDR) gene polymorphismsand colorectal cancer risk in conjunction with potentially protective effects of calcium and vitamin D. In a studyof 685 cases of colorectal cancer and 778 community controls in Japan, we examined the associations of the FokI,BsmI, ApaI, and TaqI polymorphisms with colorectal cancer risk and effect modification by dietary calciumand vitamin D. Genotypes were determined by the PCR-RFLP method. The ApaI polymorphism seemed to beassociated with a decreased risk of colorectal cancer, particularly of rectal cancer. The adjusted odds ratio ofcolorectal cancer for the ApaI AA and Aa genotypes combined versus the aa genotype was 0.83 (95% confidenceinterval [CI] 0.67-1.02), and the corresponding value for rectal cancer was 0.75 (95%CI 0.56-0.99). A decreasedrisk of colorectal cancer for the ApaI AA and Aa genotypes combined was more evident in individuals with highcalcium intake (interaction p=0.055). The FokI polymorphism seemed to be associated with a decreased risk ofcolon cancer among those with high vitamin D intake (interaction p=0.09). The BsmI and TaqI polymorphismswere unrelated to colorectal cancer risk, and the null associations were not modified by calcium or vitamin Dintake. In conclusion, the ApaI polymorphism may be associated with a decreased risk of colorectal cancer inJapanese, dependent on dietary calcium intake.