Red meat intake interacts with a TGF-β-pathway-based polygenic risk score to impact colorectal cancer risk: Application of a novel approach for polygenic risk score construction.

ABSTRACT:

Background

High intake of red and/or processed meat are established colorectal cancer (CRC) risk factors. Genome-wide association studies (GWAS) have reported 204 variants (G) associated with CRC risk. We used functional annotation data to identify subsets of variants within known pathways and constructed pathway-based Polygenic Risk Scores (pPRS) to model pPRS x environment (E) interactions.

Methods

A pooled sample of 30,812 cases and 40,504 CRC controls of European ancestry from 27 studies were analyzed. Quantiles for red and processed meat intake were constructed. The 204 GWAS variants were annotated to genes with AnnoQ and assessed for overrepresentation in PANTHER-reported pathways. pPRS's were constructed from significantly overrepresented pathways. Covariate-adjusted

SUBMITTER: Mendez JS 

PROVIDER: S-EPMC12191096 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature