{Reference Type}: Journal Article
{Title}: The relationship between innate/adaptive immunity and gastrointestinal cancer : a multi-omics Mendelian randomization study.
{Author}: Lv CX;Zhou LP;Yang YB;Shi J;Dong FH;Wei HR;Shan YQ;
{Journal}: BMC Gastroenterol
{Volume}: 24
{Issue}: 1
{Year}: 2024 Jun 14
{Factor}: 2.847
{DOI}: 10.1186/s12876-024-03284-x
{Abstract}: <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.