The Genetic Causal Effect of Autoimmune Diseases on pan-Cancers: Evidence from Mendelian Randomization

Background: Whether autoimmune diseases caused any effects on the risk of cancers remained yet clarified. This study aimed to investigate the causal effect of autoimmune diseases on pan-cancers through mendelian randomization (MR) analysis. Method: The GWAS summary datasets of 10 autoimmune diseases were derived from the IEU or UK biobank website. The GWAS summary datasets of 39 cancers were derived from the FinnGen website. The Inverse-Variance Weighted (IVW) method was used to analyze the causal association between auto-immune diseases and pan-cancers. Results: MR analysis indicated that inflammatory bowel disease would significantly increase the risk of rectum cancer, basal cell carcinoma and skin cancer, while Crohn's disease only showed causal association with increased risk of skin cancer. Rheumatoid arthritis significantly increased the risk of thyroid gland cancer, while reduce the risk of overall cancers and 7 other types of cancer outcomes. Ankylosing spondylitis showed causal relationship with increased risk of overall cancers and 5 other types of cancer outcomes. Multiple sclerosis significantly increased the risk of overall cancers and 5 other types of cancer outcomes, while reduce the risk of pancreas cancer (P=0.04). Parkinson's disease significantly reduced the risk of rectum cancer and skin cancer. Systemic lupus erythematosus significantly increased the risk of 3 types of cancer, while reduced the risk of kidney and urinary tract cancer. Psoriasis significantly increased the risk of head neck and oral cavity cancer, while reduced the risk of 3 other types of cancer. Conclusion: This study provides novel genetic epidemiological evidence linking several autoimmune diseases to various cancer, both retrospective studies and basic research on this topic should carefully consider the genetic susceptibility to autoimmune diseases in relation to cancer, including potential risk and protective factors. These findings may inform preventive strategies and treatment approaches.