Causal relationship between rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and risk of prostate cancer: Multivariable and bidirectional Mendelian-randomization analyses

Previous studies have suggested an association between autoimmune diseases (AIDs) and the risk of prostate cancer (PCa). However, the causal relationship between AID and PCa remained unclear. The purpose of this study was to investigate the causal association between 3 common AIDs, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS), and the risk of PCa. We used genome-wide association studies summary statistics to conduct forward and reverse Mendelian randomization (MR) in a two-sample framework. We also incorporated risk factors, including smoking and obesity, in the multivariable MR analysis. Multiple sensitivity analysis methods have been adopted to test the robustness of our results. Our univariable MR analysis showed that genetically predicted RA was associated with an increased risk of PCa (odds ratio: 1.036, 95% CI: 1.022-1.049, P < .001). However, there was no significant association between SLE or AS and PCa. The multivariable MR analysis adjusted for smoking and obesity confirmed the positive association between RA and PCa, but not for the other 2 autoimmune diseases. In the reverse MR analysis, we did not find any significant inverse causal associations between PCa and the 3 autoimmune diseases. Our study suggested that genetically predicted RA was likely causally associated with an increased risk of PCa, while there is no significant causal relationship between SLE or AS and PCa. These findings provided new insights into the relationship between autoimmune diseases and PCa and might inform future research and clinical practice.