Causal relationship between benign prostatic hyperplasia and prostate cancer: a bidirectional Mendelian randomization...

Area of Science:

• Genetics and Epidemiology
• Urological Oncology

Background:

• Observational studies present conflicting evidence on the relationship between benign prostatic hyperplasia (BPH) and prostate cancer (PCa).
• Mendelian randomization (MR) offers a method to investigate causality using genetic variants as instrumental variables (IVs).

Purpose of the Study:

• To investigate the causal relationship between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using a two-sample Mendelian randomization (MR) approach.
• To explore potential bidirectional causality between BPH and PCa at a genetic level.

Main Methods:

• Utilized genome-wide association studies (GWAS) data for BPH and PCa from the IEU database.
• Employed various MR methods including Inverse Variance Weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode.
• Assessed horizontal pleiotropy and heterogeneity using MR-Egger intercept and Cochran's Q test, respectively. Reverse causality was also examined.

Main Results:

• Genetically predicted BPH was significantly associated with an increased risk of PCa (IVW: OR = 1.38 × 10^7, P = 2.08 × 10^-4).
• Reverse MR analysis indicated that PCa also increased the risk of BPH (IVW: OR = 1.0011, P = 0.0031).
• Sensitivity analyses confirmed heterogeneity but no significant horizontal pleiotropy, supporting the robustness of the findings.

Conclusions:

• This study provides genetic evidence for a significant bidirectional causal relationship between BPH and an elevated risk of PCa.
• Findings suggest that individuals diagnosed with BPH could benefit from enhanced prostate cancer screening protocols.
• The genetic link underscores the importance of considering BPH status in PCa risk assessment and management strategies.