The association between CCND1 G870A polymorphism and colorectal cancer risk: A meta-analysis

BACKGROUND: CyclinD1 (CCND1) is a key cell cycle regulatory protein. A large number of epidemiological studies have assessed the potential correlation between the CCND1 G870A polymorphism and the risk of colorectal cancer (CRC), but their findings have been inconsistent. To obtain a more precise understanding of the association between the G870A polymorphism in the CCND1 gene and the CRC risk, we conducted a more comprehensive meta-analysis. METHODOLOGY: We searched PubMed, Ovid, Springer, Weipu, China National Knowledge Infrastructure (CNKI), and Wanfang databases, covering all publications (the last search was updated on January 10, 2017). The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from a fixed effect or random effect model. Statistical analyses were performed using Review Manager 5.3 and STATA 10.0 software. RESULTS: A total of 7276 CRC patients and 9667 controls from 27 publications were included in this meta-analysis. We found that compared with GG homozygote genetic model, AA, AG, AA + AG genetic models of the CCND1 G870A polymorphism were significantly associated with overall CRC risk (AA homozygote genetic model: OR = 1.28, 95% CI = 1.10–1.49; AG heterozygote genetic model: OR = 1.15, 95% CI = 1.06–1.25; AA homozygote + AG heterozygote genetic model: OR = 1.19, 95% CI = 1.07–1.33). Subgroup analyses by ethnicity and cancer location showed that A carriers were consistently associated with a significantly increased risk of CRC in all subsets of participants (Asian and Caucasian; colon cancer and rectal cancer). When stratified by study design, we found a significant association in hospital-based studies (HB), but no significant associations were found in either population-based studies (PB) or family-based studies (FB). According to subgroup analysis by cancer type, the risk of sporadic colorectal cancer (sCRC) and hereditary nonpolyposis colorectal cancer (HNPCC) were not correlated with the CCND1 G870A polymorphism, except AG (AG vs GG: OR = 1.30, 95% CI = 1.11–1.53). CONCLUSIONS: This meta-analysis suggests that the CCND1 G870A polymorphism is associated with an increased risk of CRC, especially that A carriers may be a major risk factor for CRC.