Associations between CTLA-4+49 A/G (rs231775) polymorphism and cancer risk: a meta-analysis based on 52 case-control studies

Objectives: To date, a number of epidemiological studies have explored the association between CTLA-4 +49 A/G polymorphism and cancer risk with elusive results. To address this gap, we carried out a comprehensive meta-analysis. Design and methods: Two reviewers independently searched the PubMed, EMBASE, CBM (Chinese BioMedical Disc) and China National Knowledge Infrastructure (CNKI) Databases for relevant studies up to December 20, 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) for CTLA-4 +49 A/G polymorphism and cancer risk were used to evaluate the strength of association. Results: A total of 52 case-control studies were ultimately recruited. Our results showed the statistical evidence of an association between the CTLA-4 + 49 A/G polymorphism and decreased risk of overall cancer in all the comparison models. In stratified analyses by cancer type, ethnicity and the origin of cancer, significant decreases in cancer risk were observed in breast cancer, lung cancer, other cancers epithelial tumor and Asians. In addition, in a stratified analysis by the system of cancer, significant decreases in cancer risk were found for reproductive and breast cancer, respiratory system cancer, and malignant bone tumor in all the genetic models, and other system cancer in two genetic models: GG+AG vs. AA and GG vs. AA. Conclusions: This meta-analysis suggests that the CTLA-4 +49 A/G polymorphism may be a protective factor for cancer.