Associations between circulating metabolites and pca: a bidirectional two-sample Mendelian randomization study.

Area of Science:

• Genetics
• Metabolomics
• Epidemiology

Background:

• Prostate cancer (PCa) is a globally prevalent male cancer.
• Genetic factors are crucial, but circulating metabolites also significantly influence PCa risk.
• The causal relationship between metabolites and PCa requires further clarification.

Purpose of the Study:

• To investigate the causal relationships between circulating metabolites and prostate cancer (PCa) risk.
• To identify specific metabolites that causally influence PCa development.
• To provide genetic evidence for understanding PCa etiology and developing therapeutic targets.

Main Methods:

• Employed a bidirectional two-sample Mendelian randomization (MR) approach.
• Utilized metabolite datasets from CLSA, KORA, and TwinsUK studies, and PCa data from Oncoarray.
• Performed replication analysis using UK Biobank and sensitivity analyses for robustness.

Main Results:

• Identified causal links between circulating metabolites and PCa risk.
• Found 4-ethylphenylsulfate causally associated with PCa (OR 0.66, 95% CI 0.47-0.92, p=0.015), remaining significant after Bonferroni adjustment.
• Reverse MR showed causal relationships of PCa to homovanillate and X-12,627 levels.

Conclusions:

• Findings underscore PCa etiology and risk factors.
• Provides genetic evidence for potential therapeutic targets and diagnostic biomarkers.
• Contributes to elucidating PCa disease mechanisms.