Comprehensive Analysis of 29,464 Cancer Cases and 35,858 Controls to Investigate the Effect of the Cytotoxic T-Lymphocyte Antigen 4 Gene rs231775 A/G Polymorphism on Cancer Risk

Hongyuan Wan; Hangsheng Zhou; Yanyan Feng; Yongquan Chen; Lijie Zhu; Yuanyuan Mi

doi:10.3389/fonc.2022.878507

Comprehensive Analysis of 29,464 Cancer Cases and 35,858 Controls to Investigate the Effect of the Cytotoxic T-Lymphocyte Antigen 4 Gene rs231775 A/G Polymorphism on Cancer Risk

Front Oncol. 2022 May 4:12:878507. doi: 10.3389/fonc.2022.878507. eCollection 2022.

Authors

Hongyuan Wan^{1

2}, Hangsheng Zhou^{1

2}, Yanyan Feng^{1

2}, Yongquan Chen^{3

4}, Lijie Zhu², Yuanyuan Mi²

Affiliations

¹ Wuxi Medical College, Jiangnan University, Wuxi, China.
² Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi, China.
³ Wuxi School of Medicine, Jiangnan University, Wuxi, China.
⁴ School of Food Science and Technology, Jiangnan University, Wuxi, China.

Abstract

In our previous studies, we found that the rs231775 polymorphism of cytotoxic T-lymphocyte antigen 4 (CTLA-4) is associated with risks of different cancer types; however, the association remains controversial and ambiguous, so we conducted an in-depth meta-analysis to verify the association. A complete search of the PubMed, Google Scholar, Embase, Chinese databases, and Web of Science was conducted without regard to language limitations, covering all publications since November 20, 2021. The search criteria for cancer susceptibility associated with the polymorphism in the CTLA-4 gene rs231775 resulted in 87 case-control studies with 29,464 cases and 35,858 controls. The association strength was analyzed using odds ratios and 95% confidence intervals. Overall, we found that the CTLA-4 rs231775 polymorphism may reduce cancer risk. A stratified cancer type analysis showed that CTLA-4 rs231775 polymorphism was a risk factor for colorectal cancer and thyroid cancer; on the other hand, it was a protective factor for breast cancer, liver cancer, cervical cancer, bone cancer, head and neck, and pancreatic cancer. We also classified cancer into five systems and observed an increased association with digestive tract cancer, decreased associations with orthopedic tumors, tumors of the urinary system, and gynecological tumors. In the subgroup based on race, decreased relationships were observed in both Asians and Caucasians. The same decreased association was also shown in the analysis of the source of control analysis. Our present study indicates that the CTLA-4 rs231775 polymorphism contributes to cancer development and aggression.

Keywords: cancer; cytotoxic T-lymphocyte antigen 4; meta-analysis; polymorphism; tumor marker.