Association between autoimmune disorders and prostate cancer: a Mendelian Randomization Study

Abstract Background: Although many epidemiological studies or meta-analyses have reported an association between autoimmune disorders and prostate cancer, no studies have reported a clear causal relationship and the direction of the association. The purpose of our research was to explore the potential causal relationship between autoimmune disorders and prostate cancer through mendelian randomization study(MR). Method: We retrieve literature through the pubmed using key words of "Autoimmune disorder" AND "cancer", and find that more than ten autoimmune disorders and cancer are potentially related. We continue to use the keywords of “autoimmune disorder” AND “prostate cancer” to find more clues on the correlation between prostate cancer and autoimmune disease. According to the above literature support, we selected 16 common autoimmune disorders that may be associated with prostate cancer. We extracted and selected disease-related single nucleotide polymorphisms (SNPs) from the largest and public genome-wide association study (GWAS) summary data. Inverse variance weighted (IVW) method was applied as our primary analyses for the two-sample Mendelian randomization and multivariate mendelian randomization analysis to estimate the OR value and 95% confidence interval. In addition, we conducted other two analyses to verify the reliability of the conclusion: weighted median method and MR-Egger method. We further verified the robustness of the conclusions by a series of sensitivity analyses. Results: The autoimmune diseases we selected included rheumatoid arthritis, ankylosing spondylitis, coxarthrosis, gonarthrosis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary sclerosing cholangitis, asthma, type I diabetes, systemic lupus erythematosus, multiple sclerosis, autoimmune hyperthyroidism, psoriatic arthritis, and polymyalgia rheumatica. The results of IVW methods suggest that six immune diseases have been associated with the development of prostate cancer. Three diseases that may be significantly associated with higher risk of prostate cancer are rheumatoid arthritis (OR: 1.03, 95%CI,1.01-1.05, p=0.001), coxarthrosis (OR: 1.17, 95%CI,1.08-1.26, p < 0.001), and gonarthrosis (OR: 1.17, 95%CI,1.05-1.3, p=0.008). Three possible protective factors for prostate cancer are primary sclerosing cholangitis (OR: 0.97, 95%CI,0.95-0.99, p=0.001), autoimmune hyperthyroidism (OR: 0.97, 95%CI,0.94-0.99, p=0.011), and psoriatic arthritis (OR: 0.97, 95%CI,0.95-0.99, p=0.001). Multivariate Mendelian randomization found no association between Crohn's disease or ulcerative colitis and prostate cancer. Horizontal pleiotropy was not found in MR-Egger intercepts. Conclusion: Our findings provide genetic predictive evidence of an association between autoimmune disorders and prostate cancer, and these findings have important implications for screening and management in clinical practice.