Objectives Matrix metalloproteinases (MMPs) are implicated in tissue remodeling and inflammation, yet their causal roles in prostate diseases remain unclear. This study employed two‐sample Mendelian randomization (MR) to investigate genetic evidence for causal relationships between MMPs and prostate diseases. Materials and Methods First, univariable MR (UVMR) was used to assess the causal effects of ten genetically predicted MMPs on four prostate diseases. Genetic instruments for MMPs were derived from genome‐wide association study (GWAS) catalog data, while prostate disease outcomes were sourced from FinnGen R12. Inverse variance weighted (IVW), MR‐Egger, weighted median, and weighted mode methods were applied. For robust associations, multivariable MR (MVMR) was performed to investigate the mediating effects of key inflammatory markers. Sensitivity analyses included Cochran’s Q , MR‐PRESSO, and leave‐one‐out tests. Results In the UVMR analysis, genetically predicted higher levels of MMP9 were causally associated with a modest, but statistically significant, increased risk of benign prostatic hyperplasia (BPH; odds ratio OR = 1.052, 95% confidence interval CI: 1.019–1.085, p = 0.0015). This was the only association to survive false discovery rate (FDR) correction ( q < 0.10). Nominal associations were observed for MMP10 with prostatitis and MMP12 with malignant prostate neoplasm. Critically, in the MVMR analysis, the causal effect of MMP9 on BPH was substantially attenuated and became nonsignificant after adjusting for genetically predicted levels of C‐reactive protein (OR = 1.046, 95% CI: 0.983–1.114, p = 0.152) and other inflammatory mediators. Conclusion This study provides robust genetic evidence supporting a causal relationship between elevated MMP9 levels and the risk of BPH, which appears to be largely mediated by inflammatory pathways.
Cai et al. (Thu,) studied this question.