CTLA-4 polymorphisms and predisposition to digestive system malignancies: a meta-analysis of 31 published studies

Abstract

Background The results of genetic association studies regarding cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) polymorphisms and digestive system malignancies were controversial. The authors designed this meta-analysis to more precisely estimate relationships between CTLA-4 polymorphisms and digestive system malignancies by pooling the results of related studies. Methods The authors searched PubMed, Embase, Web of Science, and CNKI for eligible studies. Thirty-one eligible studies were pooled analyzed in this meta-analysis. Results The pooled meta-analysis results showed that genetic distributions of rs231775, rs4553808, and rs733618 polymorphisms among patients with digestive system malignancies and controls differed significantly. Moreover, genotypic distribution differences were also observed for rs231775 polymorphism among patients with colorectal cancer/pancreatic cancer and controls, for rs4553808 and rs5742909 polymorphisms among patients with gastric cancer and controls, for rs3087243 polymorphism among patients with liver cancer and controls, and for rs733618 polymorphism among patients with colorectal cancer and controls in pooled meta-analyses. Conclusions This meta-analysis suggested that rs231775 polymorphism was associated with predisposition to colorectal cancer and pancreatic cancer, rs4553808 and rs5742909 polymorphisms were associated with predisposition to gastric cancer, rs3087243 polymorphism was associated with predisposition to liver cancer, and rs733618 polymorphism was associated with predisposition to colorectal cancer.

Immune Checkpoint Molecules—Inherited Variations as Markers for Cancer Risk

“…Due to discrepancies observed in aforementioned publications future well designed studies are needed to resolve ambiguities between published results. For CTLA-4c.-1722T>C , CTLA-4c.-1661A>G , CTLA-4c.-319C>T , and CTLA-4CT60G>A , there was no evidence of associations with CRC risk ( 94 , 114 ).…”

“…This meta-analysis showed that in the Chinese population the CTLA-4c.49 A/A genotype increased the risk of HCC of about 1.5-fold. On the other hand, the most recent meta-analysis by Li et al ( 94 ) [analyzing data included in work by Wang et al ( 101 ), except one study published in Chinese language ( 104 ), and data from two additional studies ( 105 , 106 )], did not confirm previous observations and suggested a lack of association between the CTLA-4c.49A>G and HCC risk.…”

“…This finding is inconsistent with results for other types of cancer, where the CTLA-4c.-319*T allele has been identified as a tumor risk factor. Additionally, this meta-analysis indicated that the carriage of the CTLA-4c.-1661*A allele may predispose to GC development (OR = 1.78) ( 94 ).…”

“…The most recent meta-analysis published in 2020 ( 94 ) which relates to digestive system malignancies (among them gastric cancers) summarizes the results from available studies concerning the following CTLA-4 SNPs: CTLA-4c.-1772T>C , CTLA-4c.-1661A>G , CTLA-4c.-319C>T , CTLA-4c.49A>G , CTLA-4CT60G>A and gastric cancer (GC) risk ( 38 , 95 – 100 ). According to this meta-analysis, CTLA-4c.49A>G was not associated with GC risk, despite the fact that such association was demonstrated in some of individual studies included in this analysis.…”

“…The most recent meta-analysis by Li et al ( 94 ) [analyzing data from 8 out of 11 reports included in paper by Zhang et al ( 113 )] reported that CTLA-4c.49 G/G genotype decreased risk of colorectal cancer about 1.8 times in comparison to G/A and A/A genotypes. Due to discrepancies observed in aforementioned publications future well designed studies are needed to resolve ambiguities between published results.…”