Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
DNA Cell Biol. 2011 Dec;30(12):1051-5. doi: 10.1089/dna.2011.1269. Epub 2011 May 25.
Despite the knowledge of many genetic alterations present in osteosarcoma, the complexity of this disease precludes placing its biology into a simple conceptual framework. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays important roles in downregulating T-cell activation, thereby attenuating anti-tumor responses and increasing cancer susceptibility. Polymorphisms in the CTLA-4 gene are associated with different autoimmune diseases and cancers. The current study evaluated the association of four CTLA-4 gene mutations, -1661A/G (rs4553808), -318C/T (rs5742909), +49G/A (rs231775), and CT60A/G (rs3087243), with osteosarcoma in the Chinese population. CTLA-4 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 267 osteosarcoma patients and 282 age-matched healthy controls. Results showed that the CTLA-4 gene +49 AA genotype, +49 A allele, and GTAG haplotype were significantly more frequent in osteosarcoma patients than in controls (odds ratio [OR] 2.20, 95% confidence interval [CI] 1.23-2.95, p = 0.007; OR 1.32, 95% CI 1.03-1.69, p = 0.029, and OR = 1.47, 95% CI 1.03-2.09, p = 0.033, respectively). The CTLA-4 +49G/A polymorphism and GTAG haplotype are associated with increased risk of osteosarcoma.
尽管人们已经了解了骨肉瘤中存在的许多基因改变，但这种疾病的复杂性使得其生物学特征难以被纳入一个简单的概念框架中。细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）在下调 T 细胞激活方面发挥着重要作用，从而减弱了抗肿瘤反应并增加了癌症易感性。CTLA-4 基因的多态性与不同的自身免疫性疾病和癌症有关。本研究评估了 CTLA-4 基因的四个突变，-1661A/G（rs4553808）、-318C/T（rs5742909）、+49G/A（rs231775）和 CT60A/G（rs3087243）与中国人群骨肉瘤之间的关联。通过聚合酶链反应-限制性片段长度多态性检测了 267 例骨肉瘤患者和 282 例年龄匹配的健康对照者的 CTLA-4 多态性。结果显示，CTLA-4 基因+49 AA 基因型、+49 A 等位基因和 GTAG 单倍型在骨肉瘤患者中比对照组更为常见（比值比 [OR] 2.20，95%置信区间 [CI] 1.23-2.95，p=0.007；OR 1.32，95% CI 1.03-1.69，p=0.029，OR=1.47，95% CI 1.03-2.09，p=0.033）。CTLA-4+49G/A 多态性和 GTAG 单倍型与骨肉瘤风险增加相关。
