Causal role of immune cells in digestive system cancers: A Mendelian randomization study

Abstract Background: Immune cell characteristics and digestive system cancers (DSCs) are correlated; however, the causal relationship between immune cell phenotypes and DSCs remains unclear. In this study, a comprehensive two-sample Mendelian randomization (MR) analysis was performed based on publicly available genetic data to investigate the causal relationship between 731 immunophenotypes and the risk of esophageal cancer (EC), gastric cancer (GC), hepatocellular cancer (HCC), gallbladder cancer, small intestine cancer, colorectal cancer (CRC), and pancreatic cancer (PCA) development. Methods: Inverse variance weighting (IVW), MR-Egger regression, and weighted median methods were used for the MR analysis. Results: IVW results confirmed that among the 731 immunophenotypes, three, six, two, two, four, and five immunophenotypes had significant causal effects on the development of GC, HCC, gallbladder cancer, small intestine cancer, CRC, and PCA, respectively. However, immunophenotypes with a significant causal relationship with EC were not found. Moreover, the instrumental variables did not exhibit significant heterogeneity or horizontal pleiotropy. Conclusions: This MR study demonstrated a close association between immune phenotype and DSCs through genetic means and could guide future clinical studies.