Causal plasma metabolites for breast cancer risk: a two-sample Mendelian randomization study with colocalization evidence.

ABSTRACT:

Background

Breast cancer pathogenesis involves complex metabolic dysregulation, yet causal biomarkers remain elusive. This study aimed to assess causal effects of 1,400 human plasma metabolites on breast cancer (BC) risk using a two-sample Mendelian randomization (MR) framework.

Methods

We employed a rigorous two-sample Mendelian randomization framework with tiered quality control (Bonferroni correction, sensitivity analyses, meta-analyses) to investigate causal metabolite-BC associations. Colocalization (PPH4 > 0.80) and phenome-wide MR (2,099 FinnGen phenotypes) validated mechanistic specificity and clinical safety profiles.

Results

Five genetically determined plasma metabolites were identified as the potential causal biomarkers for BC risk: 3,5-dichloro-2,6-dihydro

SUBMITTER: Chen H 

PROVIDER: S-EPMC12534670 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature