Association of Cytotoxic T-lymphocyte Antigen-4 Polymorphisms with Malignant Bone Tumors Risk A Meta-analysis

Background Previous studies have assessed the association between the Cytotoxic T-lymphocyte Antigen- 4(CTLA-4) polymorphism with the risk of malignant bone tumor, but the conclusions were inconsistent. We aimed to clarify association of cytotoxic T-lymphocyte antigen-4 polymorphisms with malignant bone tumors risk by performing a meta-analysis. Materials and Methods The databases including PubMed, EMBase databases and the Cochrane Library were searched to identify the eligible studies prior to January 30 2016. Odds ratio (OR) with 95% con dence interval (95%CI) were used to estimate the strengths of the association between the CTLA-4 polymorphism and the malignant bone tumor risks. The meta-analysis was performed by STATA 12.0. Results Four individual studies with a total of 1003 cases with malignant bone tumor and 1162 controls were included in our meta-analysis. The results of meta-analysis on those data demonstrated that CTLA-4 +49G>A polymorphism was associated with the risk of Ewing's sarcoma and osteosarcoma strongly (A vs. G OR1.36, 95%CI1.20- 1.54, p0.000; AA+AG vs. GG OR1.35, 95%CI1.14-1.61, p0.001; AA vs. GG OR2.24, 95%CI1.67-2.99, p0.000; AA vs. AG+GG OR2.00, 95%CI1.53-2.62, p0.000), but CTLA-4 -318C/T polymorphism was not associated with the risk of malignant bone tumor (C vs. T OR0.76, 95%CI0.76-1.08, p 0.262; CC+CT vs. TT OR0.70, 95%CI0.41-1.20, p0.198; CC vs. TT OR0.69, 95%CI0.40-1.19, p 0.183; CC vs. CT+TT OR0.92, 95%CI0.75-1.13, p 0.419). Subgroup analysis showed that there are signi cantly positive correlations between CTLA-4 +49G>A polymorphism and increased risks of malignant bone tumors in large size of sample (A vs. G OR1.347, 95%CI 1.172,1.548, p0.000; AA vs. GG OR2.228, 95%CI 1.608,3.085, p0.000), Ewing's Sarcoma or Osteosarcoma (A vs. G OR1.361, 95%CI 1.201,1.540, p0.000; AA vs. GG OR2.236, 95%CI 1.674,2.986, p0.000), and PCR-RFLP or Sequencing(A vs. G OR1.361, 95%CI 1.201,1.540, p0.000; AA vs. GG OR2.236, 95%CI 1.674,2.986, p0.000), but CTLA-4 -318C/T polymorphism was not associated with the risk of malignant bone tumors in diagnosis, genotype method, and sample size (all p>0.05). Conclusions CTLA-4 +49A/G variant was associated with an increased risk of developing the malignant bone tumors, such as Ewing's sarcoma and osteosarcoma. However, it failed to show the association between CTLA-4 -318C/T polymorphism and the risk of malignant bone tumors. Future large-scale studies remain to be done to con rm our conclusions.