Blood metabolites, mitochondrial biofunction, and cervical cancer: a bidirectional Mendelian randomization study

Area of Science:

• Oncology
• Metabolomics
• Mitochondrial Biology

Background:

• Cervical cancer development is linked to blood metabolites and mitochondrial function, but causal links remain unclear.
• Investigating these associations is crucial for understanding cancer etiology and developing targeted therapies.

Purpose of the Study:

• To investigate the potential causal relationships between blood metabolites, mitochondrial biofunction, and cervical cancer using a bidirectional two-sample Mendelian randomization approach.
• To identify specific metabolites and biofunctions that may influence cervical cancer risk or act protectively.

Main Methods:

• Utilized Mendelian randomization with single nucleotide polymorphisms (SNPs) as instrumental variables.
• Employed Inverse Variance Weighted (IVW), MR Egger, and Weighted Median methods for robust causal inference.
• Conducted sensitivity and subgroup analyses, alongside metabolic pathway analysis using MetaboAnalyst 6.0.

Main Results:

• Identified 25 blood metabolites and 3 mitochondrial biofunctions with potential causal links to cervical cancer.
• Discovered distinct risk and protective factors across different pathological types of cervical cancer.
• Linolenic acid metabolism, particularly Linolenate, demonstrated significant anti-tumor potential (OR=0.81, 95% CI: 0.67-0.99).

Conclusions:

• Blood metabolites and mitochondrial biofunctions are causally associated with cervical cancer.
• Findings provide novel insights into cervical cancer etiology and potential therapeutic targets.
• Highlights the role of lipid metabolism, specifically linolenic acid, in cervical cancer development.