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

Ryan C. Lewis, Roberd M. Bostick, Dawen Xie, Zonglin Deng, Michael J. Wargovich, Michael F. Fina, Walter M. Roufail, Kim R. Geisinger

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Cyclin D1, encoded by the CCND1 gene and activated by the adenomatous polyposis coli-β-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.

Original languageEnglish (US)
Pages (from-to)8549-8553
Number of pages5
JournalCancer Research
Volume63
Issue number23
StatePublished - Dec 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Polymorphism of the Cyclin D1 Gene, CCND1, and Risk for Incident Sporadic Colorectal Adenomas'. Together they form a unique fingerprint.

Cite this