Abstract
PurposeCTLA-4 is one of the most fundamental immunosuppressive cotykines which belongs to the immunoglobulin super-family, and is expressed mainly on activated T cells. Previous studies have reported the existence of CTLA4 60G/A and CTLA4 -1661A/G polymorphism in cancers. However, the effects remain conflicting. Hence, we performed a meta-analysis to investigate the association between these polymorphisms and cancer risk.MethodsWe searched the Pubmed and Web of Science databases until October 24, 2013 to obtain relevant published studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the relationship between CTLA4 gene polymorphisms and cancer susceptibility were calculated by stata 11 software. Heterogeneity tests, sensitivity analyses and publication bias assessments were also performed in our meta-analysis.ResultsA total of 22 articles comprising 31 case-control studies concerning the CTLA-4 60G/A and CTLA-4 -1661A/G polymorphisms were included in the meta-analysis. The pooled results suggested the CTLA-4 60G/A polymorphism was significantly associated with an increased skin cancer risk (AA vs. GG: OR = 1.32, 95%CI = 1.09-1.59; AA vs. GA+GG: OR = 1.26, 95%CI = 1.07-1.48). For CTLA-4 -1661 A/G polymorphism, the results showed that the CTLA-4 -1661A/G polymorphism was significantly associated with an increased cancer risk (GA vs. AA: OR = 1.44, 95%CI = 1.13–1.82; GA+GG vs. AA: OR = 1.35, 95%CI = 1.07–1.69; G vs. A: OR = 1.21, 95%CI = 1.01–1.47), especially in gastric cancer, breast cancer, other cancers and in Asians population subgroups.ConclusionOur meta-analysis suggests that the CTLA-4 -1661A/G polymorphism is a potential factor for the susceptibility of cancer, especially in gastric cancer, breast cancer and other cancers, and the CTLA-4 60G/A polymorphism is significantly associated with increased skin cancer risk. The effect of the CTLA-4 -1661A/G polymorphism on cancer susceptibility especially exists in Asians and population based subjects.
Highlights
Cancer is a major cause of death in most countries, and it is estimated that the number of new cases of patients will be more than 15 million in the coming decade, creating a substantial worldwide public health burden [1]
The pooled results suggested the Cytotoxic T lymphocyte antigen-4 (CTLA-4) 60G/A polymorphism was significantly associated with an increased skin cancer risk (AA vs. GG: OR = 1.32, 95%confidence intervals (CIs) = 1.09-1.59; AA vs. GA+GG: OR = 1.26, 95%CI = 1.07-1.48)
For CTLA-4 -1661 A/G polymorphism, the results showed that the CTLA-4 -1661A/G polymorphism was significantly associated with an increased cancer risk (GA vs. AA: OR = 1.44, 95%CI = 1.13–1.82; GA+GG vs. AA: OR = 1.35, 95%CI = 1.07–1.69; G vs. A: OR = 1.21, 95%CI = 1.01–1.47), especially in gastric cancer, breast cancer, other cancers and in Asians population subgroups
Summary
Cancer is a major cause of death in most countries, and it is estimated that the number of new cases of patients will be more than 15 million in the coming decade, creating a substantial worldwide public health burden [1]. Researches have shown that cancer is the result of complex interactions in many factors, especially between inherited and environmental factors [2]. It has been velar that genetic variation is an important factor contributes to the development and progression of cancer, and an increasing number of studies have focused on the interactions between genetic factors and cancer susceptibility [3]. T-cell activation threshold, thereby attenuating the antitumor response and increasing cancer susceptibility [8]. Among the CTLA-4 gene polymorphisms, two polymorphisms including CTLA4 60G/A (rs3087243) in the 3’-UTR, and CTLA4 -1661A/G (rs4553808) in promoter region were widely studied and have been reported to be associated with susceptibility to inflammatory diseases, autoimmune diseases and cancers [9,10]
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