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Loïc Le Marchand, MD, PhD; Ann Seifried, BA; Annette Lum-Jones, BS; Timothy Donlon, PhD; Lynne R. Wilkens, DrPH

JAMA. 2003;290:2843-2848.

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.

Author Affiliations: Cancer Research Center of Hawaii, University of Hawaii, Honolulu.

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