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The following is a summary of “Mediation Effects of Metabolites and Sex Hormones on the Relationship between Body Mass Index and Breast Cancer: Mendelian Randomization Analysis and Mediation Analysis,” published in the October 2024 issue of Oncology by Yang et al.
Observational studies indicate a strong correlation between body mass index (BMI) and breast cancer (BC), but the underlying biological pathways remain unclear.
Researchers conducted a retrospective study to investigate the causal relationship between BMI and breast cancer and identify potential mediators.
They utilized Mendelian randomization analysis (Inverse Variance Weighted model) on extensive cohorts from publicly available genome-wide association studies (GWAS) of population from Europe, assessing heterogeneity and horizontal pleiotropy.
The results showed significant negative causal relationships between BMI and BC, estrogen receptor-positive breast cancer (ER+BC), and estrogen receptor-negative breast cancer (ER-BC). Specifically, 35 metabolites, 33 metabolites and sex hormones, and 15 metabolites mediated the causal effects of BMI on BC, ER+BC, and ER-BC, respectively. BMI increases ER+BC risk via the pathway of sex hormones (biologically available testosterone) and decreases BC risk through multiple metabolite pathways.
They concluded that BMI influences breast cancer risk through both sex hormones and various metabolites, suggesting potential avenues for preventive strategies and interventions.
Source: frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1449956/abstract
