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.


CONCLUSIONS
Variants in the CASR intracellular signaling region were significantly associated with the risk of advanced adenoma.
Peters
Ulrike
U
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA. upeters@fhcrc.org
Chatterjee
Nilanjan
N
Yeager
Meredith
M
Chanock
Stephen J
SJ
Schoen
Robert E
RE
McGlynn
Katherine A
KA
Church
Timothy R
TR
Weissfeld
Joel L
JL
Schatzkin
Arthur
A
Hayes
Richard B
RB
D000236:Adenoma / Q000209:etiology / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D004032:Diet; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011897:Random Allocation; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D012307:Risk Factors; D012812:Sigmoidoscopy
D044169:Receptors, Calcium-Sensing