Polymorphism of the cyclin D1 gene, CCND1, and risk for incident sporadic colorectal adenomas.
Cyclin D1, encoded by the CCND1 gene and activated by the adenomatous polyposis coli-beta-catenin-T-cell factor/lymphoid enhancing factor pathway, induces G(1) 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 (>or=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.
Lewis
Ryan C
RC
Department of Epidemiology and Biostatistics, Norman J Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA.
Bostick
Roberd M
RM
Xie
Dawen
D
Deng
Zonglin
Z
Wargovich
Michael J
MJ
Fina
Michael F
MF
Roufail
Walter M
WM
Geisinger
Kim R
KR
D000236:Adenoma / Q000235:genetics*; D000483:Alleles; D002455:Cell Division / Q000235:genetics; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D011110:Polymorphism, Genetic
D019938:Cyclin D1