Cytotoxic T-lymphocyte antigen 4 polymorphisms and breast cancer susceptibility: Evidence from a meta-analysis

Background:Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an immune checkpoint and regulates the immune function of T cells. However, previous findings regarding the association of CTLA-4 polymorphisms and breast cancer remain inconclusive. Therefore, we performed a meta-analysis to investigate the potential effects of five polymorphisms (-1722 T/C, -1661 A/G -318 C/T, +49 A/G, and CT60 A/G) in the CTLA-4 gene on breast cancer susceptibility. Methods:Relevant literatures were systematically searched through electronic databases including PubMed, EMBASE, and Web of Science up to October 10, 2021. Available data were extracted and odds ratios (ORs) with 95% confidence intervals were used to estimate the pooling effect size. The Newcastle-Ottawa Scale was applied for assessing the quality of included studies. We conducted subgroup analyses based on ethnicity and control sources to explore levels of heterogeneity. Moreover, sensitivity analysis and publication bias were assessed. Results:Finally, a total of 12 eligible studies regarding CTLA-4 polymorphisms and breast cancer were included. For overall analyses, only the +49 A/G polymorphism was significantly associated with breast cancer under allelic (OR = 1.19), dominant (OR = 1.27), and recessive (OR = 1.27) models. Ethnicity-based subgroup analysis found that the +49 A/G polymorphism has a significant risk (OR = 2.03) of breast cancer under the recessive model in the non-Asian population. Studies with hospital-based controls showed that the +49 A/G polymorphism has significant breast cancer risks under allelic (OR = 1.44), dominant (OR = 1.86), and recessive (OR = 1.60) models. In addition, those with population-based controls found that -1722 T/C polymorphism has a significant breast cancer risk under allelic (OR = 1.19) and dominant (OR = 1.26) models. Conclusion:This meta-analysis suggested that CTLA-4 + 49 A/G polymorphism may significantly associate with breast cancer susceptibility. Future studies containing various populations are helpful for evaluating the impacts of CTLA-4 polymorphisms on breast cancer susceptibility.