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.

Association of Five Snps in Cytotoxic T-Lymphocyte Antigen 4 and Cancer Susceptibility: Evidence from 67 Studies

“…Previous meta-analyses have discussed the association of CTLA-4 polymorphisms with cancer risk [83-85]. To the best of our knowledge, we are the first to perform such a comprehensive meta-analysis of the common functional polymorphisms of the CTLA-4 gene comprising all the published and well-defined case-control studies.…”

IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients

“…Numerous studies have shown the association of CTLA-4 polymorphisms with allograft rejection, endstage renal disease, delayed graft function and infection after renal transplantation [29][30][31][32] , and the expression pattern of the protein encoded by CTLA4 was found to be altered by the polymorphisms rs4553808 (-1661A/G) in the CTLA4 gene promoter [33] . It is reported that a carry of G allele variation will increase CTLA4 mRNA level and expression, thereby promoting consensus sequence in the regulatory region of the CTLA4 promoter in humans [26,34] . The result of our study revealed that polymorphism of rs4553808 (-1661A/G) in CTLA4 gene promoter may influence TAC dose requirement.…”

Lack of any Association of the CTLA-4 +49 G/A Polymorphism with Breast Cancer Risk in a North Indian Population

“…It causes a 17Thr to 17Ala substitution in the leading peptide of CTLA-4 receptor. Its role in increasing cancer susceptibility is well known in various populations across the world, especially Asians (Geng et al, 2013). The effect of SNPs on cancer susceptibility differs in different ethnic populations and there is no data till date with respect to the effect of this SNP on breast cancer susceptibility in our North Indian population.…”

“…On one hand it is known to increase the susceptibility of various autoimmune diseases and on the other hand it is also known to be associated with susceptibility and aggressiveness of various cancers (Ghaderi et al, 2011;Geng et al, 2013). Its role in skin cancer is well documented and we now even have a drug (Ipilimumab) against this important molecular target (Blank, 2014).…”