Association between cytotoxic T lymphocyte antigen-4 +49A/G, −1722T/C, and −1661A/G polymorphisms and cancer risk: a meta-analysis

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.