Significant association between cytotoxic T lymphocyte antigen 4 +49G>A polymorphism and risk of malignant bone tumors

Cytotoxic T lymphocyte antigen 4 (CTLA-4) gene +49G>A polymorphism was implicated to be associated with risk of malignant bone tumors, but the finding was inconclusive owing to the limited sample of a single study. The objective of the current study was to conduct a pooled analysis of four previously published studies to investigate the association between CTLA-4 +49G>A polymorphism and the risk of malignant bone tumors. Data were extracted, and the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) was calculated to assess the association. Those four published studies included a total of 2,165 subjects. The pooled results indicated that CTLA-4 +49G>A polymorphism was significantly associated with risk of malignant bone tumors (AA versus GG: OR = 2.24, 95 % CI 1.67–2.99, P < 0.001; AA/GA versus GG: OR = 1.35, 95 % CI 1.14–1.61, P = 0.001; AA versus GG/GA: OR = 2.00, 95 % CI 1.53–2.62, P < 0.001). Stratified analyses by tumor type showed that CTLA-4 +49G>A polymorphism was associated with risks of both osteosarcoma (AA versus GG: OR = 2.23, 95 % CI 1.45–3.43, P < 0.001; AA/GA versus GG: OR = 1.35, 95 % CI 1.04–1.75, P = 0.024; AA versus GG/GA: OR = 2.00, 95 % CI 1.34–2.98, P = 0.001) and Ewing's sarcoma (AA versus GG: OR = 2.24, 95 % CI 1.51–3.31, P < 0.001; AA/GA versus GG: OR = 1.36, 95 % CI 1.07–1.72, P = 0.011; AA versus GG/GA: OR = 2.01, 95 % CI 1.39–2.89, P < 0.001). Therefore, results from the current pooled analysis suggest that CTLA-4 +49G>A polymorphism is associated with risk of malignant bone tumors, including osteosarcoma and Ewing's sarcoma.