Cyclin D1 G870A Polymorphism Contributes to Colorectal Cancer Susceptibility: Evidence from a Systematic Review of 22 Case-Control Studies

BACKGROUND: Cyclin D1 (CCND1) plays a vital role in cancer cell cycle progression. Numerous epidemiological studies have evaluated the association between the CCND1 G870A polymorphism and the risk of colorectal cancer. However, these studies have yielded conflicting results. To derive a more precise estimation of this association, we conducted a meta-analysis and systematic review. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive search was conducted to identify eligible studies of the CCND1 G870A polymorphism and colorectal cancer risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from a fixed effect or random effect model. We applied a grading system (Venice criteria) that assessed the epidemiological strength of the association. A total of 22 publications that included 6157 cases and 8198 controls were identified. We found that the CCND1 G870A polymorphism was significantly associated with overall colorectal cancer risk (homozygote genetic model: OR = 1.130, 95% CI = 1.023–1.248, P = 0.016; heterozygote genetic model: OR = 1.124, 95% CI = 1.030–1.226, P = 0.009; dominant genetic model: OR = 1.127, 95% CI = 1.037–1.224, P = 0.005). After further stratified analyses, the increased risk was observed only in the subgroups of hospital-based studies, PCR-RFLP genotyping methods, sporadic colorectal cancer, and Caucasian ethnicity. CONCLUSIONS: The available evidence demonstrates that the CCND1 870A allele might be a low-penetrant risk factor for colorectal cancer.