Associations between serum metabolites and female cancers: A bidirectional two-sample mendelian randomization study

Area of Science:

• Metabolomics
• Oncology
• Genetic Epidemiology

Background:

• Female cancers (breast, ovarian, cervical, endometrial) pose significant global health challenges.
• Current genetic information inadequately explains the complex etiology of these cancers.

Purpose of the Study:

• To investigate causal associations between serum metabolites and four major female cancers using a bidirectional two-sample Mendelian randomization approach.
• To identify potential metabolic biomarkers for female cancer risk, detection, and progression.

Main Methods:

• Utilized Mendelian randomization (MR) with Wald ratio, inverse-variance weighted, MR-Egger, and weighted median methods.
• Employed sensitivity analyses (Cochrane's Q, Egger's intercept, MR-PRESSO, leave-one-out) for robustness.
• Analyzed data from Canadian Longitudinal Study of Aging, Finngen, Cancer Association Consortium, and Leo's studies.

Main Results:

• Identified causal associations between specific metabolites (e.g., 3-hydroxyoleoylcarnitine, hexadecanedioate) and breast cancer.
• Found causal links between certain steroid sulfates (e.g., androsterone sulfate) and endometrial cancer.
• Reverse MR analysis revealed causal relationships between various cancers/survival and multiple metabolites.

Conclusions:

• Specific serum metabolites play potential roles in the etiology of female cancers.
• These metabolites may serve as novel biomarkers for early detection, risk stratification, and monitoring disease progression.
• Further research can explore metabolite-specific pathways in cancer development for prevention and treatment strategies.