CTLA-4 polymorphisms associate with breast cancer susceptibility in Asians: a meta-analysis

PeerJ. 2017 Jan 10:5:e2815. doi: 10.7717/peerj.2815. eCollection 2017.

Abstract

Previous studies have investigated the association between cytotoxic T-lymphocyte antigen-4 (CTLA-4) polymorphisms and breast cancer susceptibility, but the results remained inconsistent. Therefore, we evaluated the relationship between four common CTLA-4 polymorphisms and breast cancer risk by a meta-analysis, aiming to derive a comprehensive and precise conclusion. We searched EMBASE, Pubmed, Web of Science, CNKI, and Wanfang databases until July 18th, 2016. Finally, ten eligible studies involving 4,544 breast cancer patients and 4,515 cancer-free controls were included; all these studies were from Asia. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the breast cancer risk in five genetic models. The results indicated that the CTLA-4 +49A>G (rs231775) polymorphism had a significant association with decreased breast cancer risk in allelic, homozygous, dominant and recessive models. Also, the +6230G>A (rs3087243) polymorphism reduced breast cancer risk especially in the Chinese population under homozygous and recessive models. In contrast, the -1661A>G (rs4553808) polymorphism increased breast cancer risk in allelic, heterozygous and dominant models, whereas -1722 T>C (rs733618) did not relate to breast cancer risk. In conclusion, CTLA-4 polymorphisms significantly associate with breast cancer susceptibility in Asian populations, and different gene loci may have different effects on breast cancer development. Further large-scale studies including multi-racial populations are required to confirm our findings.

Keywords: Breast cancer; CTLA-4; Meta-analysis; Polymorphism; Susceptibility.

Grants and funding

This study was supported by the National Natural Science Foundation, China (No. 81471670); the China Postdoctoral Science Foundation (No. 2014M560791; 2015T81037); the Fundamental Research Funds for the Central Universities, China (No. 2014qngz-04) and the Science and Technology Plan of Innovation Project, Shaanxi province, China (No. 2015KTCL03-06). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.