Genetically predicted benign prostate hyperplasia causally affects prostate cancer: a two-sample Mendelian...

Area of Science:

• Urology
• Oncology
• Genetics

Background:

• Benign prostate hyperplasia (BPH) and prostate cancer (PCa) share risk factors like age and androgen dependency.
• A causal link between BPH and PCa has not been previously established.
• Investigating potential causal associations is crucial for understanding disease progression.

Purpose of the Study:

• To explore the potential causal relationship between BPH and PCa using a two-sample Mendelian randomization (MR) design.
• To leverage genetic data to infer causality between these common prostate conditions.
• To identify if genetic predisposition to BPH influences the risk of developing PCa.

Main Methods:

• Utilized genome-wide association study (GWAS) data for BPH and PCa from large European ancestry cohorts.
• Employed a two-sample MR design with single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs).
• Applied inverse-variance-weighted (IVW) method and sensitivity analyses (MR-Egger, leave-one-out) to ensure result validity.

Main Results:

• Genetically predicted BPH showed a statistically significant causal association with an increased risk of PCa (1.02-fold increase, P<0.001).
• The association remained robust across sensitivity analyses, indicating no significant heterogeneity or pleiotropy.
• Findings provide strong genetic evidence for a causal link between BPH and PCa risk.

Conclusions:

• This study provides the first genetic evidence supporting a causal relationship between BPH and an elevated risk of PCa.
• BPH may be a contributing factor in the development of PCa, warranting further investigation.
• Findings could inform clinical management, including screening and treatment strategies for BPH patients to mitigate PCa risk.