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Polymorphism of the Cyclin D1 Gene, CCND1, and Risk for Incident Sporadic Colorectal Adenomas

¹ Department of Epidemiology and Biostatistics, Norman J. Arnold School of Public Health, University of South Carolina, Columbia, South Carolina;
² Departments of Family and Preventive Medicine and
³ Pathology and Microbiology, School of Medicine, University of South Carolina, Columbia, South Carolina;
⁴ Forsyth Medical Center, Piedmont Gastroenterology Specialists, Winston-Salem, North Carolina; and
⁵ Departments of Medicine and
⁶ Pathology, Wake Forest University, School of Medicine, Winston-Salem, North Carolina

Cyclin D1, encoded by the CCND1 gene and activated by the adenomatous polyposis coli-ß-catenin-T-cell factor/lymphoid enhancing factor pathway, induces G₁ to S-phase cell cycle transition, promoting cell proliferation. A recently described codon 242, exon 4, G to A single nucleotide polymorphism (A870G) produces a longer half-life cyclin D1. To investigate whether CCND1 genotype influences risk for colorectal adenoma, we genotyped CCND1 by PCR/RFLP on 161 incident sporadic adenoma cases and 213 controls ages 30–74 years in a North Carolina colonoscopy-based case-control study. At least one polymorphic A allele was found in 68% of cases and 60% of controls. Having an A allele was associated with increased risk for adenoma: the age- and sex-adjusted odds ratio (OR) was 1.5 [95% confidence interval (CI) 1.0–2.4], a finding that was stronger for those whose adenomas were multiple (OR 2.9, 95% CI 1.4–6.0), larger (1 cm; OR 2.4, 95% CI 1.2–4.8), had moderate to severe dysplasia (OR 2.1, 95% CI 1.1–3.8), or were in the right side of the colon (OR 3.6, 95% CI 1.3–10.0). Joint risk factor multivariate analyses revealed stronger positive associations among those who were older (>57 years; OR 2.8, 95% CI 1.4–5.5), male (OR 2.8, 95% CI 1.3–5.7), currently smoked (OR 2.7, 95% CI 1.3–5.7), or currently drank alcohol (OR 2.2, 95% CI 1.2–4.2) if they had an A allele and stronger inverse associations among those who used nonsteroidal anti-inflammatory drugs (OR 0.4, 95% CI 0.2–0.9) or had higher calcium intakes (OR 0.4, 95% CI 0.2–0.9) if they had no A allele. These data support the hypothesis that the CCND1 A870G polymorphism may increase risk for colorectal neoplasms.

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