The causal relationship between ankylosing spondylitis and the risk of ovarian cancer

Objective: The aim of this study was to investigate the potential causal relationship between ankylosing spondylitis (AS) and ovarian cancer. Methods: We conducted analyses utilizing publicly available pooled statistical data sets from genomewide association studies (GWAS) involving individuals of European ancestry. Our objective was to identify single nucleotide polymorphisms (SNPs) significantly associated with AS and use them as instrumental variables to assess the causal relationship between AS and ovarian cancer. We employed three statistical methods for twosample Mendelian randomization: inverse variance weighting (IVW), weighted median, and MR-Egger regression. Network MR Analysis revealed the mediating role of tumor necrosis factor receptor superfamily member 21 between ankylosing spondylitis and ovarian cancer. Results: From the GWAS on AS, we selected 23 instrumental SNPs that exhibited genome-wide significance. Our findings consistently demonstrated an association between AS and ovarian cancer using multiple statistical methods (IVW: odds ratio (OR) 1.147, 95% confidence interval (CI) 1.022-1.287; weighted median estimator: OR 1.177, 95% CI 1.009-1.373; MR-Egger regression: OR 1.166, 95% CI 0.958-1.418). These results indicate a positive correlation, suggesting that AS is associated with an increased risk of ovarian cancer. Furthermore, there was no evidence to suggest that the observed causal effect between AS and the risk of osteoarthritis was influenced by genetic pleiotropy (MR-Egger intercept = -0.0010644, P = 0.8433359). In addition, tumor necrosis factor receptor superfamily member 21 mediated 10.2% of the total effect size in the development of ankylosing spondylitis on ovarian cancer risk. Conclusion: Our Mendelian randomization analysis provides strong evidence supporting a potential causal relationship between AS and ovarian cancer risk, with ankylosing spondylitis clearly associated with an increased risk of ovarian cancer. Tumor necrosis factor receptor superfamily member 21 as a mediator involved in the occurrence and development of these two diseases.