This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Peters, U. Articles by Hayes, R. B. Search for Related Content PubMed PubMed Citation Articles by Peters, U. Articles by Hayes, R. B.

Association of Genetic Variants in the Calcium-Sensing Receptor with Risk of Colorectal Adenoma

¹ Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland; ² Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington;³ Department of Epidemiology, University of Washington, Seattle, Washington; ⁴ Department of Health and Human Services, Core Genotype Facility, National Cancer Institute, NIH, Gaithersburg, Maryland; ⁵ University of Pittsburgh, Pittsburgh, Pennsylvania; and ⁶ Division of Environmental and Occupational Health, University of Minnesota, Minneapolis, Minnesota

Requests for reprints: Ulrike Peters, Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M4-B402 Seattle, WA 98109-1024. Phone: 206-667-2450; Fax: 206-667-7850. upeters{at}fhcrc.org

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.

Key Words: calcium sensing receptor • CASR • colorectal adenoma • colorectal cancer • polymorphism