Abstract
BACKGROUND: Although many epidemiological studies and meta-analyses have reported an association between autoimmune disorders and prostate cancer, none has reported a clear correlation or the direction of the association. The purpose of our study was to explore the potential relationship between autoimmunity-related disorders and prostate cancer using Mendelian randomization (MR). METHODS: We retrieved literature from PubMed using the keywords "autoimmune disorder" AND "prostate cancer" to find more clues on the correlation between prostate cancer and autoimmunity-related disorder. Based on this literature search, we selected 16 autoimmunity-related disorders that had genome-wide association study (GWAS) data and may be associated with prostate cancer. The inverse variance weighting (IVW) method was applied as our primary analysis for two-sample MR and multivariate MR analysis to estimate the odds ratio (OR) and 95% confidence interval (CI). We further verified the robustness of our conclusions using a series of sensitivity analyses. RESULTS: The autoimmunity-related diseases selected include rheumatoid arthritis, ankylosing spondylitis, coxarthrosis, gonarthrosis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary sclerosing cholangitis, asthma, type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, autoimmune hyperthyroidism, psoriatic arthropathies, and polymyalgia rheumatica. The results of inverse variance weighting (IVW suggested that six diseases were associated with the development of prostate cancer. The three diseases that may increase the risk of prostate cancer are rheumatoid arthritis (P = 0.001), coxarthrosis (P < 0.001), and gonarthrosis (P = 0.008). The three possible protective factors against prostate cancer are primary sclerosing cholangitis (P = 0.001), autoimmune hyperthyroidism (P = 0.011), and psoriatic arthropathies (P = 0.001). Horizontal pleiotropy was not observed in the MR-Egger test. CONCLUSIONS: Our findings provide predictive genetic evidence for an association between autoimmune disorders and prostate cancer. Further research is needed to explore the underlying mechanisms of comorbidities at the molecular level.