title: Association between cytotoxic T lymphocyte antigen-4 +49A/G, -1722T/C, and -1661A/G polymorphisms and cancer risk: a meta-analysis.
abstract: Cytotoxic T lymphocyte antigen-4 (CTLA-4), a key gene that contributes to the susceptibility and clinical course of cancer, is an important down-regulator of T cell activation and proliferation. The +49A/G polymorphism is commonly studied because of its association with cancer risks. However, other polymorphisms, such as -1722T/C and -1661A/G, have not been studied in detail. We performed a meta-analysis using 43 eligible case-control studies with a total of 19,089 patients and 21,388 controls to examine the association between CTLA-4 +49A/G, -1722T/C, and -1661A/G polymorphisms and cancer risk. We searched the PubMed and EMBASE databases for all articles published up to July 17, 2013. Individuals with the +49 A allele (AA/AG vs. GG, odds ratio (OR) = 1.21, 95% confidence interval (95% CI) = 1.16-1.27) and -1661 G allele (AG/GG vs. AA, OR = 1.52, 95% CI = 1.34-1.73) had increased cancer risk. However, no significant association between cancer risk and the -1722T/C polymorphism was found (CC/CT vs. TT, OR = 1.04, 95% CI = 0.92-1.16). In subgroup analysis for the +49A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR = 1.25, 95 % CI = 1.18-1.31), patients with breast cancer (OR = 1.28, 95% CI = 1.15-1.42), and patients with lung cancer (OR = 1.20, 95 % CI = 1.07-1.35). For the -1661A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR = 1.52, 95% CI = 1.34-1.73), patients with breast cancer (OR = 1.48, 95% CI = 1.07-2.03), and patients with oral cancer (OR = 3.16, 95% CI = 1.84-5.45). However, no significant increase in cancer risk was found in the subgroups for the -1722T/C polymorphism. In conclusion, the results suggest that +49A/G and -1661A/G polymorphisms in CTLA-4 are risk factors for cancers, whereas the -1722T/C polymorphism is not associated with an increased risk of cancer.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China, njmugengrui@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Geng
authors.forename: Fanglong
authors.initials: F
authors.lastname: Song
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Junzheng
authors.initials: J
authors.lastname: Hu
authors.forename: Chunhui
authors.initials: C
authors.lastname: Zhu
authors.forename: Binjie
authors.initials: B
authors.lastname: Zhu
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
mesh_terms: D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human