Genetically Predicted 1400 Blood Metabolites in Relation to Risk of Prostate Cancer: A Mendelian Randomization Study.

Area of Science:

• Oncology
• Metabolomics
• Genetic Epidemiology

Background:

• Metabolic dysregulation is frequently observed in cancer development.
• Limited evidence currently links circulating metabolites to causal pathways in prostate cancer (PCa).

Purpose of the Study:

• To investigate potential causal relationships between circulating blood metabolites and prostate cancer (PCa) risk.
• To leverage Mendelian randomization (MR) analysis for evaluating metabolite associations with PCa.

Main Methods:

• A two-sample Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) data for 1400 blood metabolites and PCa.
• Data included 462,933 individuals for metabolite GWAS and UK Biobank data (79,148 cases, 61,106 controls) for PCa GWAS.
• Inverse variance weighting (IVW) was the primary analysis method, supplemented by MR-Egger and weighted median, with comprehensive sensitivity analyses for robustness.

Main Results:

• A significant inverse association was identified between Cysteinylglycine disulfide levels and prostate cancer (PCa) risk.
• The association showed a consistent trend in validation analyses, and sensitivity analyses confirmed the robustness of the findings.

Conclusions:

• Circulating Cysteinylglycine disulfide levels may play a causal role in modulating prostate cancer (PCa) risk.
• These findings contribute to understanding the metabolic underpinnings of PCa development.