Vitamin D receptor polymorphism and the risk of colorectal adenomas: Evidence of interaction with dietary vitamin D and calcium

Laboratory studies and epidemiological investigations suggest that vitamin D plays a role in the etiology of colorectal adenomas, possibly through a m echanism mediated by the vitamin D receptor (VDR). We conducted a clinic-ba sed case-control study to examine the association between VDR polymorphisms and colorectal adenomas. We selectively identified a random subset of 393 cases of colorectal adenomas and 406 colonoscopy-negative controls from a c linic-based case-control study conducted in the metropolitan Minneapolis/St . Paul area during 1991-1994. A self-administered questionnaire was used to collect data on dietary and supplement intake of vitamin D and calcium, as well as on demographics, physical activity, medical information, lifestyle factors, reproductive history, and anthropometry. DNA was extracted from w hole blood and assayed for the BsmI VDR polymorphism using an ABI 7700 TaqM an assay. Adjusted odds ratios (OR) and 95% confidence intervals (Cls) were evaluated using logistic regression. Compared with the bb genotype (33% of controls), neither the Bb (48.8% of controls) nor the BB (18.2% of control s) genotypes was strongly associated with risk of colorectal adenomas (OR = 0.86, CI = 0.63-1.19 and OR = 0.77, CI = 0.50-1.18, respectively). However , those with the lowest tertile of vitamin D intake and the BB genotype had a lower risk of colorectal adenoma (OR 0.24, CI = 0.08-0.76) than those wi th the highest tertile of intake and the bb genotype. Similarly, those with the lowest tertile of calcium intake and the BB genotype had a reduced ris k of colorectal adenoma (OR = 0.34, Cl 0.11-1.06). Although it has generall y been shown that higher calcium and vitamin D intake are associated with a modestly reduced risk of colorectal neoplasia, our data suggest that those with the BB BsmI VDR genotype may be at reduced risk of colorectal adenoma in the presence of lower calcium and vitamin D intake.