Association between cytotoxic T-lymphocyte antigen-4 polymorphisms and lung cancer susceptibility: Evidence from a meta-analysis

Abstract Background: The relationship between cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene polymorphisms and lung cancer risk has been investigated in many studies, with inconclusive findings. Objectives: We performed a comprehensive meta-analysis to evaluate the effects of CTLA-4 polymorphisms (−318C/T, +49A/G, and CT60 A/G) on lung cancer susceptibility. Methods: Eligible studies were searched from PubMed, EMBASE, Web of Science, and the Cochrane Library. Odds ratios with their 95% confidence intervals were calculated to assess the combined effect sizes. Subgroup analyses were conducted based on ethnicity and histology. The levels of heterogeneity, sensitivity, and publication bias were also assessed. Statistical analyses were performed by Review Manager Version 5.4. Results: This study finally included eight case–control studies from eight eligible articles, with one study providing two separate datasets comprising the CTLA-4 polymorphisms (−318C/T, +49A/G, and CT60A/G) and lung cancer were included. No significant associations were found between CTLA-4 polymorphisms and lung cancer in the allele, dominant, or recessive models. For the +49A/G polymorphism in the subgroup analysis, significantly decreased lung cancer risks of 0.86 (0.74–1.00) and 0.72 (0.54–0.97) were found for subjects with the G allele and under the dominant model, respectively. Conclusion: Based on the limited studies, we observed no significant relationships between CTLA-4 polymorphisms (−318C/T, +49A/G, and CT60 A/G) and the risk of lung cancer. However, those with the G allele and G/G + G/A genotype have significantly decreased risks of lung cancer in the subgroup analysis. More functional genetic variations with a larger sample are needed to clarify the potential effects of CTLA-4 polymorphisms on the development of lung cancer in the future.