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

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.

Association between the side effect induced by COVID-19 vaccines and the immune regulatory gene polymorphism

“…We focused on the promoter region of genes, because the SNP located in the promoter region may affect the expression level of gene ( 17 ). In addition, the hot points of autoimmune diseases and cancer types were considered, including rs231775 in exon1 of CTLA4 ( 18 , 19 ), rs3087243 in 3 prime untranslated region (3’UTR) of CTLA4 ( 19 ) and rs11568821 in intron4 of PDCD1 ( 20 ). Thus, eight fragments were selected for SNP analysis.…”

CTLA4 genetic variants associated with urothelial bladder cancer susceptibility

“…The most studied CTLA4 variant in UBC is rs231775 (+ 49A > G) and is also related to kidney, breast, liver and lung cancer (Guo et al, 2015;Isitmangil et al, 2016;Fang et al, 2018;Wei et al, 2021;Wan et al, 2022). In this variant there is an exchange of Adenine for Guanine at position 49 which leads to the exchange of the amino acid threonine for alanine in the CTLA-4 protein, which has a higher a nity for binding to B7.1 than CTLA-4 coded by the A allele.…”

Winners of the 2023 honor awards for excellence at the annual meeting of the Chinese Medical Association-Taipei: Part II

“…15 Wang's group found the association between rs231775 polymorphism of CTLA-4 and risks of different cancer types remains controversial and ambiguous, and therefore, they conducted an in-depth meta-analysis to verify the association. 16 The results showed that CTLA-4 rs231775 polymorphism was associated with increased colorectal cancer and thyroid cancer; but by contrast, it was a negative correlation to the development of breast cancer, liver cancer, cervical cancer, bone cancer, head and neck, and pancreatic cancer. 16 Additionally, an analysis of association between variants of CTLA-4 and cancer risk based on race, decreased relationships were observed in both Asians and Caucasians and the same decreased association was also shown in the analysis of the source of control analysis, 16 which seemed to be against Dr. Chang's finding to show the significant relationships between "A" allele in rs231775 (+49 A/G polymorphism) and increased breast cancer risk of East Asian individuals.…”

“…16 The results showed that CTLA-4 rs231775 polymorphism was associated with increased colorectal cancer and thyroid cancer; but by contrast, it was a negative correlation to the development of breast cancer, liver cancer, cervical cancer, bone cancer, head and neck, and pancreatic cancer. 16 Additionally, an analysis of association between variants of CTLA-4 and cancer risk based on race, decreased relationships were observed in both Asians and Caucasians and the same decreased association was also shown in the analysis of the source of control analysis, 16 which seemed to be against Dr. Chang's finding to show the significant relationships between "A" allele in rs231775 (+49 A/G polymorphism) and increased breast cancer risk of East Asian individuals. 8 Although the final conclusion made by Wang's group indicates that the CTLA-4 rs231775 polymorphism contributes to cancer development and aggression, the debate and argument about the association between variants of CTLA-4 and cancer risk are still unsolved.…”