Cytotoxic T-lymphocyte antigen-4 polymorphisms and susceptibility to Ewing's sarcoma.

The development of Ewing's sarcoma (ES) is a complex process, resulting from interplay between mutations in oncogenes and tumor suppressors, host susceptibility factors, and cellular context. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays important roles in downregulating the T-cell activation. Polymorphisms in the CTLA-4 gene have been shown to be associated with different autoimmune diseases and cancers. The current study evaluated the association of two CTLA-4 gene polymorphisms, -318C/T (rs5742909) and +49G/A (rs231775) with ES in the Chinese population. CTLA-4 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 223 ES cases and 302 age-matched healthy controls. Data were analyzed using the chi-square test. Results showed that prevalence of the CTLA-4 gene +49AA genotype and +49A allele were significantly increased in ES patients compared to controls (odds ratio [OR]=2.03, 95% confidence interval [CI], 1.13-3.66, p=0.018; and OR=1.33, 95%CI, 1.03-1.72, p=0.027). Also, subjects with CA (-318, +49) haplotype had a 1.37-fold increased risk to develop ES (p=0.032). In addition, ES patients with metastasis had higher numbers of +49AA genotype than those with localized cases (OR=2.66, 95%CI, 1.14-6.22, p=0.022). These results indicate that the CTLA-4+49G/A polymorphism is a new risk factor for ES and may affect the prognosis of this cancer.