Association of genetic variants in the calcium-sensing receptor with risk of colorectal adenoma

Objective: Evidence suggests that calcium prevents colorectal cancer, possibly mediated through the calcium-sensing receptor (CASR). We assessed the associations between CASR gene variants and risk for colorectal adenoma, a cancer precursor. We further investigated gene-diet interactions between the CASR variants and calcium intake on adenoma risk. Methods: Individuals with advanced distal adenomas (n = 716) and controls with a negative sigmoidoscopy exam (n = 729) were randomly selected from participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Three nonsynonymous variants in the intracellular signaling region of CASR (A986S, R990G, Q1011E) were analyzed by Taqman. Results: Compared with the most common diplotype (haplotype pair), the odds ratios for advanced adenoma were 0.80 [95% confidence interval (CI), 0.60-1.06], 0.79 (95% CI, 0.55-1.13), and 0.56 (95% CI, 0.36-0.88) for the other three common diplotypes (>5% frequency). Although calcium intake was inversely associated with adenoma risk, CASR diplotypes did not modify this association. However, the power to investigate interactions was limited. Conclusion: Variants in the CASR intracellular signaling region were significantly associated with the risk of advanced adenoma.