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. 2024 Dec 19;19(1):129.
doi: 10.1186/s13062-024-00575-x.

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

Yi Wang #  1   2 , Guihua Chen #  2 , Deng Li #  2 , Dongliang Zhang  3 , Qianwei Xing  4
Affiliations

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

Yi Wang et al. Biol Direct. .

Abstract

Background: 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.

Purpose: We first took advantage of Mendelian randomization to clarify this issue and provide clinical implications for these patients' populations.

Methods: 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.

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.

Conclusion: 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.

Keywords: Benign Prostatic Hyperplasia; Clinical implications; Mendelian randomization; Prostate Cancer; Prostatitis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: None declared. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The whole study design
Fig. 2
Fig. 2
Two-sample Mendelian randomization results in the discovery dataset
Fig. 3
Fig. 3
Two-sample Mendelian randomization results in the validation dataset
Fig. 4
Fig. 4
Mediator Mendelian randomization analyses and clinical implications for (A) prostatitis; (B) BPH; (C) PCa patients’ populations
Fig. 5
Fig. 5
Disease patterns map
See this image and copyright information in PMC

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