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

Author:

Chang Hao-Yun12,Liu Chao-Yu3,Lo Yen-Li4,Chiou Shih-Hwa5678,Lu Kai-Hsi9,Lee Ming-Cheng10,Wang Yuan-Hung1112

Affiliation:

1. School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC

2. Division of General Medicine, Department of Medical Education, Far Eastern Memorial Hospital, New Taipei City, Taiwan, ROC

3. Division of Traumatology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan, ROC

4. Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan, ROC.

5. Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC

6. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC

7. Stem Cell & Genomic Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC

8. Genomic Research Center, Academia Sinica, Taipei, Taiwan, ROC

9. Department of Medical Research and Education, Cheng-Hsin General Hospital, Taipei, Taiwan, ROC

10. Division of Infectious Diseases, Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan, ROC

11. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC

12. Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC

Abstract

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

General Medicine

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