Prostatitis, benign prostatic hyperplasia, and prostate cancer: a bidirectional Mendelian randomization study and clinical implications for these patients’ populations

No authoritative books or guidelines are currently available for revealing the interrelationships of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Moreover, no consensus on this issue has been reached among previously published epidemiological studies or meta-analyses. We first took advantage of Mendelian randomization to clarify this issue and provide clinical implications for these patients' populations. Bidirectional two-sample and mediator Mendelian randomization were applied to explore the causal relationships among prostatitis, BPH, and PCa. Sensitivity analyses, including phenotype scanning, heterogeneity, pleiotropy, leave-one-out analysis, and the Steiger test, were conducted to evaluate the robustness and reliability of our results. Our results revealed the interrelationships among prostatitis, BPH, and PCa via Mendelian randomization, confirming that genetic susceptibility to prostatitis or BPH could lead to increased risks of PCa directly or indirectly (P < 0.05). Moreover, mediator Mendelian randomization revealed four potential mediator pathways, including the prostatitis-BPH-PCa, the BPH-PCa-prostatitis, the PCa-prostatitis-BPH, and the PCa-BPH-prostatitis pathways. Based on these, we also provided clinical implications for prostatitis, BPH, and PCa patients' populations, respectively. Interestingly, a total of three vicious circles were revealed by us, including the prostatitis-BPH circle, the BPH-PCa circle, and the prostatitis-BPH-PCa circle. All of these three vicious circles contributed to the progression of benign prostate diseases to malignant diseases. We successfully clarified the interrelationships among prostatitis, BPH, and PCa, providing clinical implications for these patients' populations. A total of three vicious circles were also revealed by us to provide novel ideas for future drug development and guide clinical decision-making. No authoritative books or guidelines are currently available for revealing the interrelationships of prostatitis, BPH, and PCa. No consensus has been reached among previously published epidemiological studies or meta-analyses, due to their limitations. Epidemiological researches investigating this issue still had controversies, and they were often case-control or retrospective cohort studies. We first took advantage of Mendelian randomization to explore the interrelationships among prostatitis, BPH, and PCa. We provided clinical implications for prostatitis, BPH, and PCa patients' populations, respectively, based on mediator Mendelian randomization. We identified a total of three vicious circles, contributing to the progression of benign prostate diseases to malignant diseases. Our results provided novel ideas for drug development and new therapeutic strategies for clinical PCa prevention or treatment.