title: Cytotoxic T-lymphocyte antigen-4 genetic variants and risk of Ewing's sarcoma.
abstract: Despite the knowledge of many genetic alterations present in Ewing's sarcoma (ES), the complexity of this disease precludes placing its biology into a simple conceptual framework. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) can decrease T-cell activation and attenuate antitumor responses. Polymorphisms in the CTLA-4 gene have been shown to be associated with different diseases. Here, we investigated the association of four CTLA-4 gene polymorphisms, -1661A/G (rs4553808), -318C/T (rs5742909), +49G/A (rs231775), and CT60A/G (rs3087243), with ES in the Chinese population. A total of 308 ES cases and 362 healthy controls were recruited and CTLA-4 polymorphisms were tested by polymerase chain reaction-restriction fragment length polymorphism. Results showed that frequencies of the CTLA-4 gene +49AA genotype, +49A allele, and GTAG haplotype were significantly increased in ES patients compared to healthy controls (odds ratio [OR]=2.42, 95% confidence interval [CI] 1.43-4.09, p<0.001; OR 1.38, 95% CI 1.11-1.73, p=0.005, and OR=1.46, 95% CI 1.06-2.02, p=0.020, respectively). We further compared CTLA-4 polymorphisms in ES patients based on different clinical parameters and data revealed that ES patients with metastasis had higher numbers of the +49AA genotype than those without metastasis (p=0.004). These results indicated that the CTLA-4 polymorphism could be a risk factor for ES and suggested a potential role of CTLA-4 in the metastasis of this malignancy.
authors.affiliation: Spine Center, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Feng
authors.forename: Xinghai
authors.initials: X
authors.lastname: Yang
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
authors.forename: Tielong
authors.initials: T
authors.lastname: Liu
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wu
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Song
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Wenwu
authors.initials: W
authors.lastname: Gao
authors.forename: Quan
authors.initials: Q
authors.lastname: Huang
authors.forename: Wending
authors.initials: W
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Jianru
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People; D001859:Bone Neoplasms / Q000208:ethnology / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012512:Sarcoma, Ewing / Q000208:ethnology / Q000235:genetics*
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human