Critical appraisal and trial sequential meta-analysis for the association of CCND1 G870A gene polymorphism with the risk for colorectal cancer in Asian population

BACKGROUND: CCND1 gene encoding the cyclin D1 protein is critically implicated in the regulation of cell cycle and genetic alterations in the CCND1 gene are thought to increase susceptibility for cancer development by altering the pathways of cellular transition and proliferation. In particular, the association of G870A polymorphism in the CCND1 gene with the pathogenesis of colorectal cancer (CRC) has been evaluated in many studies. However, the results have been inconclusive among the Asian population. In this trial sequential meta-analysis, we attempt for a precise evaluation of the relationship between CCND1 G870A gene polymorphism with CRC risk, specifically in the Asian population. METHODS: Medline (PubMed), EMBASE (Excerpta-Medica) and Google Scholar were employed for the selection of relevant studies. The significance of association between CCND1 G870A gene polymorphism with CRC risk was determined by estimation of the Odds Ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The pooled analysis indicated no significant relationships between the allelic (A vs. G: P=0.274 OR=1.093, 95% CI=0.932-1.281), heterozygous (AG vs. GG: P=0.724; OR=1.029, 95% CI=0.876-1.209), homozygous mutant (AA vs. GG: P=0.363; OR=1.159, 95% CI=0.843- 1.595), dominant (AA + AG vs. GG: P=0.423; OR=1.101, 95% CI=0.871-1.391) and recessive (AA vs. GG+ AG: P=0.262; OR=1.126, 95% CI=0.9150-1.384) genetic models and the susceptibility for CRC. Moreover, the study showed no publication bias. CONCLUSIONS: While our meta-analysis indicates that the CCND1 G870A genetic variant may not be a risk factor for CRC development in the Asian population, larger prospective-epidemiological studies evaluating the roles of CCND1 G870A polymorphism in the etiology of CRC are required to confirm the present findings.