Comprehensive evaluation of the cytotoxic T-lymphocyte antigen-4 gene polymorphisms in risk of bone sarcoma.

Abstract

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a critical immunoregulatory molecule that attenuates the antitumor response by elevating the T-cell activation threshold, thus inducing occurrence of cancer. Several studies have reported the associations of CTLA-4 polymorphisms and bone sarcoma, but the findings remain to be further verified due to incomplete and limited evidence. The purpose of this study was to reevaluate the associations via a comprehensive meta-analysis. We searched Embase, Web of Knowledge, and PubMed and identified a total of four case-control studies fulfilling the inclusion criteria. Meta-analysis was conducted in all subjects without further stratified analyses. The associations were estimated by odds ratio (OR) along with 95% confidence interval (CI). Analysis showed a significant association for the +49G>A polymorphism. This association was more pronounced in the homozygous model (OR=1.85; 95% CI: 1.40, 2.46; p=0.998 for heterogeneity) and the recessive model (OR=1.85; 95% CI: 1.41, 2.42; p=0.959 for heterogeneity). The allele model also demonstrated statistical evidence, indicating a moderately increased risk of bone sarcoma in relation to the +49>A polymorphism (OR=1.21; 95% CI: 1.08, 1.36; p=0.996 for heterogeneity). Conversely, neither an increase or nor a decrease was observed in the genotypes of -318C>T polymorphism. Our meta-analysis provides evidence that support that the +49>A polymorphism, but not the -318C>T polymorphism, may be associated with elevated risk of bone sarcoma in Asians.