Causality between appendiceal disease and cancers of the digestive system: A Mendelian randomization study

The connection between appendiceal disease and cancers of the digestive tract has attracted widespread attention, but conclusion remain controversial. It is still unclear whether appendiceal disease has a definite causal effect on cancer. Our research aims to explore the causal relationship between appendiceal diseases and digestive system tumors. A two-sample Mendelian randomization (MR) analysis was conducted using genome-wide association study datasets to explore the causal impact of appendiceal disease on the risk of cancers. Five different MR methods were used to investigate causality. The stability, heterogeneity, and pleiotropy of MR were also assessed. The presence of appendiceal disease could reduce the incidence of rectal cancer (odds ratio = 0.588, 95% confidence interval: 0.392-0.881, P = .010, by inverse variance weighted method). There was no significant causal effect of appendiceal disease on the risk of other cancers. No horizontal pleiotropy was observed in the MR analysis, and leave-one-out analysis confirmed the stability of the results. The potential causal relationship between appendiceal disease and cancer risk was only observed with rectal cancer in populations of European ancestry. Future work will provide more robust evidence for the connection between appendiceal disease and cancers.