Association of the cyclin D1 A870G polymorphism with advanced colorectal cancer.

摘要

CONTEXT: Cyclin D1 (CCND1) is a key cell cycle regulatory protein, the overexpression of which is often found in human tumors and is associated with cell proliferation and poor prognosis. A common adenine-to-guanine substitution polymorphism (A870G) in the CCND1 gene results in an altered messenger RNA transcript and a longer-life protein, which are preferentially encoded by the A allele. OBJECTIVE: To test the overall and stage-specific associations of the CCND1 870A allele with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: A population-based case-control study conducted in the multiethnic population of Hawaii between January 1, 1994, and August 31, 1998, which included 504 patients with incident colorectal cancer and 624 population-based participants of Japanese, white, or Native Hawaiian origin. Participation rates were 58% for cases and 52% for controls.Main Outcome Measurement Ethnicity, gene-dosage effects, and stage (regional/distant) and subsite (colon vs rectal) of cancer. RESULTS: The odds ratio (OR) for the CCND1 870 GA and AA genotypes compared with the GG genotype was 1.2 (95% confidence interval [CI], 0.9-1.7) and 1.5 (95% CI, 1.0-2.1), respectively (P =.03 for gene-dosage effect). These risk estimates were significantly greater for patients diagnosed at a regional or distant stage (GA vs GG: OR, 1.7; 95% CI, 1.1-2.5 and AA vs GG: OR, 1.9; 95% CI, 1.2-3.1; P =.008 for gene-dosage effect) compared with those estimates for patients diagnosed at an earlier stage (P =.048). In subset analyses, the association between the A allele and advanced colorectal cancer was statistically significant in white and Hawaiian participants but not in Japanese, and was stronger for rectal cancer. CONCLUSION: The CCND1 870A allele may be associated with colorectal cancer, and particularly with forms of the disease that result in severe morbidity and mortality.