Replication Study and Meta-Analysis of the Contribution of Seven Genetic Polymorphisms in Immune-Related Genes to the Risk of Gastric and Colorectal Cancers

Int J Immunogenet. 2025 Jan 12. doi: 10.1111/iji.12705. Online ahead of print.

Abstract

Recently, it has been realized that immune processes participate in the pathogenesis of human cancers. A large number of genetic polymorphisms in immune-related genes have been extensively examined for their roles in the susceptibility of gastric cancer (GC) and colorectal cancer (CRC), including IL4 gene rs2070874, IL4RA gene rs1801275, IL18 gene rs187238, IL18RAP gene rs917997, IL17A gene rs8193036, IL23R gene rs1884444 and IL23R gene rs10889677. However, there is no consistent conclusion, which calls for further research. In this case-control study, these 7 genetic polymorphisms were genotyped by Sanger sequencing in a total of 1247 patients with cancer (GC/CRC: 460/787) and 800 healthy individuals. A total of 31 previous studies and our present study were included in this meta-analysis. The case-control study revealed that in Hubei Chinese population, rs2070874, rs187238 and rs10889677 were significantly associated with CRC risk, whereas only rs917997 was significantly associated with GC risk. The meta-analysis showed that rs2070874, rs917997, rs8193036 and rs1884444 were significantly associated with GC risk in Chinese population, whereas rs2070874 in total population, rs1801275 in Asian population and rs187238 in Chinese population were significantly associated with CRC risk. IL4 gene rs2070874, IL18RAP gene rs917997, IL17A gene rs8193036 and IL23R gene rs1884444 may serve as the susceptible factors for GC carcinogenesis in Chinese population. IL4 gene rs2070874 in total population, IL4RA gene rs1801275 in Asian population and IL18 gene rs187238 in Chinese population may be genetic biomarkers for CRC susceptibility.

Keywords: cancer susceptibility; case–control study; genetic polymorphism; immune‐related gene; meta‐analysis.