Yang Shufeng, Wang Chaoyang, Zhou Yujia, Sun Guojing, Zhu Dongmei, Gao Suning
Department of Orthopedics, The 81st Hospital of PLA, Nanjing, China.
Genet Test Mol Biomarkers. 2012 Oct;16(10):1236-40. doi: 10.1089/gtmb.2012.0129. Epub 2012 Aug 20.
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.
尤因肉瘤（ES）的发生是一个复杂的过程，由癌基因和肿瘤抑制基因的突变、宿主易感性因素以及细胞环境之间的相互作用导致。细胞毒性T淋巴细胞抗原4（CTLA-4）在下调T细胞活化过程中发挥重要作用。CTLA-4基因多态性已被证明与不同的自身免疫性疾病和癌症相关。本研究评估了中国人群中CTLA-4基因的两个多态性位点-318C/T（rs5742909）和+49G/A（rs231775）与ES的相关性。采用聚合酶链反应-限制性片段长度多态性方法检测了223例ES患者和302例年龄匹配的健康对照的CTLA-4多态性。使用卡方检验分析数据。结果显示，与对照组相比，ES患者中CTLA-4基因+49AA基因型和+49A等位基因的频率显著增加（优势比[OR]=2.03，95%置信区间[CI]，1.13-3.66，p=0.018；OR=1.33，95%CI，1.03-1.72，p=0.027）。此外，携带CA（-318，+49）单倍型的个体患ES的风险增加1.37倍（p=0.032）。此外，发生转移的ES患者中+49AA基因型的数量高于局限性病例患者（OR=2.66，95%CI，1.14-6.22，p=0.022）。这些结果表明，CTLA-4 +49G/A多态性是ES的一个新的危险因素，可能影响该癌症的预后。
