Exploring the Potential Link Between Autoimmune Diseases and Pan-Cancer: A Multidatabase Mendelian Randomization Analysis.

Abstract

Background: The relationship between autoimmune diseases (AIDs) and cancer is unclear and this study aimed to investigate the relationship between AIDs and cancer at the genetic level using Mendelian randomization (MR). Methods: The study employed two-sample MR and meta-analysis to investigate the association between AIDs and 33 types of cancer, following STROBE-MR guidelines. Single nucleotide polymorphisms (SNPs) associated with AIDs were used as instrumental variables, with data from FinnGen, UK Biobank, and other databases. MR analyses included sensitivity checks, heterogeneity assessments, and reverse causality tests, using multiple MR methods (inverse-variance weighted (IVW), weighted median, MR-Egger, etc.). Meta-analysis was performed on validated results to confirm findings, with statistical analyses conducted using R software. Results: The results identified eight significant associations in both discovery and replication stages. Key findings include that myasthenia gravis (MG) significantly increases the risk of oral cavity cancer, multiple sclerosis (MS) is linked to increased risks of chronic lymphocytic leukemia (CLL) and small intestine cancer, and ulcerative colitis (UC) has mixed effects, reducing the risk of uterine cervix and larynx cancers, but increasing risks for pancreatic and bladder cancers. Meta-analysis confirmed eight secondary findings, highlighting pathogenic associations such as type 1 diabetes with esophagus cancer and protective effects like systemic lupus erythematosus (SLE) against acute myelocytic leukemia. Conclusions: This study provides evidence of a causal relationship between multiple AIDs and different cancer risks at the genetic level and provides a reference for the health management of patients with AIDs.