Cytotoxic T-lymphocyte Antigen-4 Polymorphisms and Susceptibility to Osteosarcoma
Cytotoxic T-lymphocyte Antigen-4 Polymorphisms and Susceptibility to Osteosarcoma
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细胞毒性 T 淋巴细胞抗原 4 多态性与骨肉瘤易感性
DOI：
10.1089/dna.2011.1269
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发表时间：
2011-12-01
影响因子：
3.1
通讯作者：
Yuan, Wen
中科院分区：
文献类型：
--
作者：
Liu, Yang;He, Zhimin;Yuan, Wen
尽管骨肉瘤中存在许多基因改变的知识，但这种疾病的复杂性排除了将其生物学置于一个简单的概念框架中的可能性。细胞毒性T淋巴细胞抗原-4(CTLA-4)在下调T细胞活化，从而减弱抗肿瘤反应和增加肿瘤易感性方面起着重要作用。CTLA-4基因的多态与不同的自身免疫性疾病和癌症有关。本研究评估了四种CTLA-4基因突变-1661A/G(Rs4553808)、-318C/T(Rs5742909)、-49G/A(Rs231775)和CT60A/G(Rs3087243)与中国人骨肉瘤的相关性。采用聚合酶链式反应-限制性片段长度多态性方法检测267例骨肉瘤患者和282例健康对照的CTLA-4基因多态性。结果显示，CTLA4基因+49AA、+49A等位基因和GTAG单倍型在骨肉瘤患者中的分布频率显著高于对照组(OR值分别为2.20，95%可信区间1.23~2.95，p=0.007；OR1.32，95%CI1.03~1.69，p=0.029；OR值分别为1.47，95%CI1.03~2.09，p=0.033)。CTLA-4+49G/A多态和GTAG单倍型与骨肉瘤发病风险增加相关。
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.