Causal relationship between the plasma lipidome and urological cancers: A two-sample Mendelian randomization study

Area of Science:

• Metabolomics
• Oncology
• Genetics

Background:

• Plasma lipidome is associated with inflammation, obesity, aging, and cancers.
• The causal links between specific plasma lipids and urological cancer risk are not well-established.

Purpose of the Study:

• To investigate the causal relationships between 179 plasma lipid species and the risk of bladder, kidney, and prostate cancers.
• Utilize a two-sample Mendelian randomization (MR) approach for robust causal inference.

Main Methods:

• Analysis of large-scale genome-wide association study datasets for 179 lipid species.
• Employed inverse variance weighted (IVW) method, supported by MR-Egger, weighted median, and other MR techniques.
• Conducted sensitivity analyses including Cochran Q, MR-Egger intercept, MR-PRESSO, and leave-one-out analyses to ensure reliability.

Main Results:

• Elevated sterol ester (SE) (27:1/16:0) levels causally linked to increased bladder cancer risk.
• Higher phosphatidylcholine (16:0_22:6) levels associated with increased kidney cancer risk.
• Prostate cancer risk showed inverse associations with certain SE species (increased for SE (27:1/17:0), decreased for SE (27:1/18:2)).

Conclusions:

• Established strong evidence for causal links between specific plasma lipidome components and urological cancer risks.
• Findings shed light on lipid metabolism's role in urinary system cancer development.
• Results provide a basis for developing novel screening tools and targeted therapies for urological cancers.