title: Significant association between cytotoxic T lymphocyte antigen 4 +49G>A polymorphism and risk of malignant bone tumors.
abstract: Cytotoxic T lymphocyte antigen 4 (CTLA-4) gene +49G>A polymorphism was implicated to be associated with risk of malignant bone tumors, but the finding was inconclusive owing to the limited sample of a single study. The objective of the current study was to conduct a pooled analysis of four previously published studies to investigate the association between CTLA-4 +49G>A polymorphism and the risk of malignant bone tumors. Data were extracted, and the pooled odds ratio (OR) with the corresponding 95% confidence interval (95% CI) was calculated to assess the association. Those four published studies included a total of 2,165 subjects. The pooled results indicated that CTLA-4 +49G>A polymorphism was significantly associated with risk of malignant bone tumors (AA versus GG: OR = 2.24, 95% CI 1.67-2.99, P < 0.001; AA/GA versus GG: OR = 1.35, 95% CI 1.14-1.61, P = 0.001; AA versus GG/GA: OR = 2.00, 95% CI 1.53-2.62, P < 0.001). Stratified analyses by tumor type showed that CTLA-4 +49G>A polymorphism was associated with risks of both osteosarcoma (AA versus GG: OR = 2.23, 95% CI 1.45-3.43, P < 0.001; AA/GA versus GG: OR = 1.35, 95% CI 1.04-1.75, P = 0.024; AA versus GG/GA: OR = 2.00, 95% CI 1.34-2.98, P = 0.001) and Ewing's sarcoma (AA versus GG: OR = 2.24, 95% CI 1.51-3.31, P < 0.001; AA/GA versus GG: OR = 1.36, 95% CI 1.07-1.72, P = 0.011; AA versus GG/GA: OR = 2.01, 95 % CI 1.39-2.89, P < 0.001). Therefore, results from the current pooled analysis suggest that CTLA-4 +49G>A polymorphism is associated with risk of malignant bone tumors, including osteosarcoma and Ewing's sarcoma.
authors.affiliation: Department of Orthopaedic Surgery, No. 98 Hospital of PLA, No.9 Chezhan Road, Huzhou, 313000, China, fengbinpla@126.com.
authors.forename: Fengbin
authors.initials: F
authors.lastname: Yu
authors.forename: Jinhao
authors.initials: J
authors.lastname: Miao
mesh_terms: D044466:Asian People / Q000235:genetics; D001859:Bone Neoplasms / Q000208:ethnology / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D012516:Osteosarcoma / Q000208:ethnology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012512:Sarcoma, Ewing / Q000208:ethnology / Q000235:genetics
chemical_list: D060908:CTLA-4 Antigen
references.citation: Cancer. 2012 Oct 1;118(19):4681-6
references.pmid: 22359319
references.citation: Oncogene. 2012 Mar 8;31(10):1287-98
references.pmid: 21822310
references.citation: Ann Oncol. 2010 Oct;21 Suppl 7:vii320-5
references.pmid: 20943636
references.citation: Genet Test Mol Biomarkers. 2013 Jun;17(6):458-63
references.pmid: 23480667
references.citation: Clin Rheumatol. 2011 Oct;30(10):1319-24
references.pmid: 21503616
references.citation: Cancer Immunol Immunother. 2013 Feb;62(2):203-16
references.pmid: 23389507
references.citation: JAMA. 2008 May 28;299(20):2423-36
references.pmid: 18505952
references.citation: Genet Test Mol Biomarkers. 2012 Oct;16(10):1236-40
references.pmid: 22905924
references.citation: Cancer Res. 2009 Aug 1;69(15):6011-4
references.pmid: 19638588
references.citation: J Clin Epidemiol. 2003 Apr;56(4):297-303
references.pmid: 12767405
references.citation: DNA Cell Biol. 2011 Dec;30(12):1051-5
references.pmid: 21612409
references.citation: Nat Genet. 2012 Feb 12;44(3):323-7
references.pmid: 22327514
references.citation: Cancer Immunol Immunother. 2011 Aug;60(8):1137-46
references.pmid: 21465316
references.citation: Expert Opin Investig Drugs. 2011 Jul;20(7):973-9
references.pmid: 21510829
references.citation: Lancet Oncol. 2010 Feb;11(2):184-92
references.pmid: 20152770
references.citation: Gene. 2012 Nov 10;509(2):263-6
references.pmid: 22925827
references.citation: Iran J Immunol. 2011 Sep;8(3):127-49
references.pmid: 21931200
references.citation: J Bone Joint Surg Am. 2012 Oct 17;94(20):1913-9
references.pmid: 23079883
references.citation: Immunol Rev. 2008 Jun;223:143-55
references.pmid: 18613834
references.citation: PLoS One. 2011;6(10):e26060
references.pmid: 22022506
references.citation: Oncogene. 2010 Aug 12;29(32):4504-16
references.pmid: 20543858
references.citation: Genet Test Mol Biomarkers. 2011 Jul-Aug;15(7-8):503-6
references.pmid: 21453059