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http://dx.doi.org/10.14456/apjcp.2016.170/APJCP.2016.17.8.3785

Association of Cytotoxic T-lymphocyte Antigen-4 Polymorphisms with Malignant Bone Tumors Risk: A Meta-analysis  

Zhang, Chao (Department of orthopaedics, The First Hospital of Lanzhou University)
Hou, Wei-Hua (Department of orthopaedics, The First Hospital of Lanzhou University)
Ding, Xuan-Xi (Department of orthopaedics, The First Hospital of Lanzhou University)
Wang, Xiong (Department of orthopaedics, The First Hospital of Lanzhou University)
Zhao, Hui (Department of orthopaedics, The First Hospital of Lanzhou University)
Han, Xing-Wen (Department of orthopaedics, The First Hospital of Lanzhou University)
Wang, Wen-Ji (Department of orthopaedics, The First Hospital of Lanzhou University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.8, 2016 , pp. 3785-3791 More about this Journal
Abstract
Background: Previous studies have assessed the association between the Cytotoxic T-lymphocyte Antigen-4(CTLA-4) polymorphism with the risk of malignant bone tumor, but the conclusions were inconsistent. We aimed to clarify association of cytotoxic T-lymphocyte antigen-4 polymorphisms with malignant bone tumors risk by performing a meta-analysis. Materials and Methods: The databases including PubMed, EMBase databases and the Cochrane Library were searched to identify the eligible studies prior to January 30 2016. Odds ratio (OR) with 95% confidence interval (95%CI) were used to estimate the strengths of the association between the CTLA-4 polymorphism and the malignant bone tumor risks. The meta-analysis was performed by STATA 12.0. Results: Four individual studies with a total of 1003 cases with malignant bone tumor and 1162 controls were included in our meta-analysis. The results of meta-analysis on those data demonstrated that CTLA-4 +49G>A polymorphism was associated with the risk of Ewing's sarcoma and osteosarcoma strongly (A vs. G: OR=1.36, 95%CI:1.20-1.54, p=0.000; AA+AG vs. GG: OR=1.35, 95%CI:1.14-1.61, p=0.001; AA vs. GG: OR=2.24, 95%CI:1.67-2.99, p=0.000; AA vs. AG+GG: OR=2.00, 95%CI:1.53-2.62, p=0.000), but CTLA-4 -318C/T polymorphism was not associated with the risk of malignant bone tumor (C vs. T: OR=0.76, 95%CI:0.76-1.08, p= 0.262; CC+CT vs. TT: OR=0.70, 95%CI:0.41-1.20, p= 0.198; CC vs. TT: OR=0.69, 95%CI:0.40-1.19, p= 0.183; CC vs. CT+TT: OR=0.92, 95%CI:0.75-1.13, p= 0.419). Subgroup analysis showed that there are significantly positive correlations between CTLA-4 +49G>A polymorphism and increased risks of malignant bone tumors in large size of sample (A vs. G: OR=1.347, 95%CI: 1.172,1.548, p=0.000; AA vs. GG: OR=2.228, 95%CI: 1.608,3.085, p=0.000), Ewing's Sarcoma or Osteosarcoma (A vs. G: OR=1.361, 95%CI: 1.201,1.540, p=0.000; AA vs. GG: OR=2.236, 95%CI: 1.674,2.986, p=0.000), and PCR-RFLP or Sequencing(A vs. G: OR=1.361, 95%CI: 1.201,1.540, p=0.000; AA vs. GG: OR=2.236, 95%CI: 1.674,2.986, p=0.000), but CTLA-4 -318C/T polymorphism was not associated with the risk of malignant bone tumors in diagnosis, genotype method, and sample size (all p>0.05). Conclusions: CTLA-4 +49A/G variant was associated with an increased risk of developing the malignant bone tumors, such as Ewing's sarcoma and osteosarcoma. However, it failed to show the association between CTLA-4 -318C/T polymorphism and the risk of malignant bone tumors. Future large-scale studies remain to be done to confirm our conclusions.
Keywords
Cytotoxic T-lymphocyte antigen-4 (CTLA-4); Osteosarcoma; Ewing's sarcoma; Meta-analysis;
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1 Lesterhuis W J, Salmons J, Nowak A K, et al (2013). Synergistic effect of CTLA-4 blockade and cancer chemotherapy in the induction of anti-tumor immunity. PloS one, 8, 61895.   DOI
2 Liu X, Yang B, Ren H, et al (2015). Current Evidence On the Cytotoxic T-Lymphocyte Antigen 4+49G>A polymorphism and digestive system cancer risks: a meta-analysis involving 11, 923 subjects. Meta Gene, 6, 105-8.   DOI
3 Lo K L, Mertz D, Loeb M (2014). Newcastle-Ottawa Scale: comparing reviewers' to authors' assessments. Bmc Med Res Method, 14, 45.   DOI
4 Mackintosh C, Ordonez J L, Garcia-Dominguez D J, et al (2012). 1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma. Oncogene, 31, 1287-98.   DOI
5 Miller B J, Lynch C F, Buckwalter J A (2013). Conditional survival is greater than overall survival at diagnosis in patients with osteosarcoma and Ewing's sarcoma. Clin Orthop Relat R, 471, 3398-404.   DOI
6 Postel-Vinay S, Veron A S, Tirode F, et al (2012). Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma. Nat Genet, 44, 323-7.   DOI
7 Rachel W, Carroll R J (2014). Testing Hardy-Weinberg equilibrium with a simple root-mean-square statistic. Biostatistics, 15, 74-86.   DOI
8 Salvi S, Fontana V, Boccardo S, et al (2012). Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer. Cancer Immunol Immun, 61, 1463-72.   DOI
9 Silva D S B S, Sawitzki F R, De Toni E C, et al (2012). Ewing's sarcoma: analysis of single nucleotide polymorphism in the EWS gene. Gene, 509, 263-6.   DOI
10 Sun T, Zhou Y M, Hu Z, et al (2008). Functional genetic variations in cytotoxic T-lymphocyte antigen 4 and susceptibility to multiple types of cancer. Cancer Res, 68, 7025-34.   DOI
11 Yuan J, Ginsberg B, Page D, et al (2011). CTLA-4 blockade increases antigen-specific CD8+ T cells in prevaccinated patients with melanoma: three cases. Cancer Immunol Immun, 60, 1137-46.   DOI
12 Wang W, Wang J, Song H, et al (2011). Cytotoxic T-lymphocyte antigen-4 +49G/A polymorphism is associated with increased risk of osteosarcoma. Genet Test Mol Biom, 15, 503-6.   DOI
13 Yang L, Zhimin H, Dapeng F, et al (2011). Cytotoxic T-lymphocyte antigen-4 polymorphisms and susceptibility to osteosarcoma. Dna Cell Biol, 30, 1051-5.   DOI
14 Yang M, Sun T, Zhou Y, et al (2012). The functional cytotoxic T lymphocyte–associated Protein 4 49G-to-A genetic variant and risk of pancreatic cancer. Cancer, 118, 4681-86.   DOI
15 Yang S, Wang C, Zhou Y, et al (2012). Cytotoxic T-lymphocyte antigen-4 polymorphisms and susceptibility to Ewing's sarcoma. Genet Test Mol Biom, 16, 1236-40.   DOI
16 Yu F, Miao J (2013). Significant association between cytotoxic T lymphocyte antigen 4 +49G>A polymorphism and risk of malignant bone tumors. Tumour Biol, 34, 3371-5.   DOI
17 Zhang Y, Zhang J, Yao D, et al (2011). Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and cancer risk: a meta-analysis. Cancer, 117, 4312-24.   DOI
18 Benhatchi K, Jochmanova I, Habalova V, et al (2011). CTLA4 exon1 A49G polymorphism in Slovak patients with rheumatoid arthritis and Hashimoto thyroiditis-results and the review of the literature. Clinical Rheumatol, 30, 1319-24.   DOI
19 Alfadhli S, Almutawa Q, Abbas J M K, et al (2013). Association of Hashimoto's thyroiditis with cytotoxic T lymphocyteassociated antigen-4 (CTLA-4) and inducible co-stimulator (ICOS) genes in a Kuwaiti population. Endocrine, 43, 666-77.   DOI
20 Balamuth N J, Womer R B (2010). Ewing's sarcoma. Lancet Oncol, 11, 184-192.   DOI
21 Gil M A, Maside C, Cuello C, et al (2015). Osteosarcoma of the Spine: Prognostic Variables for Local Recurrence and Overall Survival, A Multicenter Ambispective Study. Mol Reprod Dev, 5, 651-63.
22 Bian Z, He Q, Wang X, et al (2014). Association of genetic polymorphisms with osteosarcoma risk: a meta-analysis. Int J Clin Exp Med, 8, 8317-28.
23 Bielack S, Carrle D, Casali P G (2009). Osteosarcoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol, 20, 137-9.   DOI
24 Feng D, Yang X, Li S, et al (2016). Cytotoxic T-lymphocyte antigen-4 genetic variants and risk of Ewing's sarcoma. Genet Test Mol Biom, 17, 458-63.
25 Hao Q, Weifeng T, Pengfei Y, et al (2013). Cytotoxic T-lymphocyte associated antigen 4 polymorphism and hashimoto's thyroiditis susceptibility: a meta-analysis. Endocrine, 45, 198-205.
26 He L, Deng T, Luo H S (2014). Association between cytotoxic T-lymphocyte antigen-4 +49A/G polymorphism and colorectal cancer risk: a meta-analysis. Int J Clin Exp Med, 8, 3752-60.
27 Hironori U, Howson J M M, Laura E, et al (2003). Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature, 423, 506-11.   DOI
28 Lang C, Chen L, Li S (2012). Cytotoxic T-lymphocyte antigen-4+ 49G/A polymorphism and susceptibility to pancreatic cancer[J]. Dna Cell Biol, 31, 683-7.   DOI
29 Huang H J, Angelo L S, Rodon J, et al (2011). R1507, an antiinsulin- like growth factor-1 receptor (IGF-1R) antibody, and EWS/FLI-1 siRNA in Ewing's sarcoma: convergence at the IGF/IGFR/Akt axis. PloS one, 6, 26060.   DOI
30 Kager L, Zoubek A, Pötschger U, et al (2003). Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol, 21, 2011-8.   DOI