Vitamin D receptor haplotypes protect against development of colorectal cancer

Abstract

We investigated the association of vitamin D receptor polymorphisms and colorectal cancer incidence in a Caucasian population. Frequencies of the vitamin D receptor gene polymorphisms 23005G>A (CDX-2), 27823C>T (FokI), 60890G>A (BsmI), 61050G>A (Tru9I), 61888G>T (ApaI), and 61968T>C (TaqI) were determined in a series of 256 colorectal cancer patients and 256 patients without malignant disease (case-control study) using polymerase chain reaction and restriction fragment length polymorphism genotyping assays (PCR-RFLP). Haplotype analysis based on the six genetic loci was applied to the received genotypes. Pairwise linkage disequilibrium between BsmI, ApaI, TaqI, and Tru9I was confirmed (P < 0.001). Allele frequencies did not differ between the groups. There was no association between any single variant and colorectal cancer. However, haplotypes BsmI(G)#TaqI(C) and BsmI(A)#TaqI(T) were inversely associated with colorectal cancer incidence (P < 0.001), the odds being 15.0 times smaller [odds ratio (OR) 0.067; 95% confidence interval (CI), 0.016-0.284] and 5.3 times smaller (OR 0.188; 95% CI 0.077-0.461), respectively, compared with noncarriers. Our findings suggest that vitamin D receptor haplotypes BsmI(G)#TaqI(C) and BsmI(A)#TaqI(T) have a protective effect against colorectal cancer in Caucasians.