%0 Journal Article
%T The relationship between innate/adaptive immunity and gastrointestinal cancer : a multi-omics Mendelian randomization study.
%A Lv CX
%A Zhou LP
%A Yang YB
%A Shi J
%A Dong FH
%A Wei HR
%A Shan YQ
%J BMC Gastroenterol
%V 24
%N 1
%D 2024 Jun 14
%M 38877387
%F 2.847
%R 10.1186/s12876-024-03284-x
%X <B>BACKGROUND: </B>Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear.<BR><B>METHODS: </B>Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes.<BR><B>RESULTS: </B>Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer.<BR><B>CONCLUSIONS: </B>This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.