Cyclin D1 (CCND1) G870A gene polymorphism is an ethnicity-dependent risk factor for digestive tract cancers: a meta-analysis comprising 20,271 subjects

Abstract

Published data on the association between Cyclin D1 (CCND1) G870A gene polymorphism and digestive tract cancers (DTC) are inconclusive. We carried out a meta-analysis of published case-control studies to derive a more precise estimation of the association. Relevant studies were identified from PubMed, EMBASE, and China National Knowledge Infrastructure up to February 1st, 2011. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to investigate the strength of the association. Data were available from a total of 33 case-control studies with 8534 cases and 11,737 controls. The combined results based on all studies showed that there was a statistically significant link between CCND1 G870A polymorphism and DTC risk (GG vs. AA: OR=0.83, 95%CI=0.71-0.96). In the analysis of ethnic groups, we found the A allele carriers had a significantly increased DTC susceptibility among Caucasians, but not among Asians. When stratified for tumor location, the results based on all studies only showed the variant allele 870A might have a significantly increased risk of colorectal cancer (CRC), especially of rectal cancer (GG vs. AA: OR=0.71, 95%CI=0.58-0.89). When stratifying by the stage and histological differentiation of CRC, we only observed that patients had a significantly higher frequency of CCND1 870 AA than non-cancer patients among Caucasians. The A allele carriers (hetero- or homozygotes) were significantly more common in cases with a family history of CRC than in controls. There was no evidence of publication bias for CCND1 G870A polymorphism with DTC risk. In summary, this meta-analysis demonstrates that the CCND1 G870A polymorphism may be an ethnicity-dependent risk factor for DTC. And this genetic variant may increase the risk of rectal cancer, but not colon cancer.