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  3. Tgf-β Pathway-based Polygenic Risk Score Modifies The Association Between Red Meat Intake And Colorectal Cancer Risk: Application Of A Novel Pathway-based Prs Method.
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  3. Tgf-β Pathway-based Polygenic Risk Score Modifies The Association Between Red Meat Intake And Colorectal Cancer Risk: Application Of A Novel Pathway-based Prs Method.

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TGF-β Pathway-Based Polygenic Risk Score Modifies the Association between Red Meat Intake and Colorectal Cancer Risk:

Joel Sanchez Mendez1, Bryan Queme2, Yubo Fu2

  • 1Department of Population and Public Health Sciences and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
|April 1, 2026

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Summary
This summary is machine-generated.

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Genetic variants in the TGF-β pathway interact with red meat consumption, influencing colorectal cancer (CRC) risk. This pathway-based polygenic risk score (pPRS) analysis reveals a significant link between specific genetic factors and dietary habits in CRC development.

Area of Science:

  • Genetics
  • Cancer Epidemiology
  • Molecular Biology

Background:

  • Red and processed meat consumption are known risk factors for colorectal cancer (CRC).
  • Genome-wide association studies (GWAS) have identified over 200 CRC risk variants.
  • Pathway-based polygenic risk scores (pPRS) can refine genetic risk assessment by integrating functional annotation data.

Purpose of the Study:

  • To construct pathway-based polygenic risk scores (pPRS) using functional annotation data.
  • To investigate interactions between pPRS and meat intake in relation to CRC risk.
  • To identify specific genetic pathways and variants involved in the meat-CRC association.

Main Methods:

  • Analyzed pooled data from 30,812 CRC cases and 40,504 controls across 27 studies.
  • Annotated 204 GWAS variants to genes and assessed pathway overrepresentation using AnnoQ and PANTHER.
  • Constructed pPRS from significantly overrepresented pathways and evaluated interactions with red/processed meat intake via logistic regression.

    • Main Results:

    • Identified 30 variants in four pathways: Presenilin-Alzheimer disease, Cadherin/WNT-signaling, Gonadotropin-releasing hormone receptor, and TGF-β signaling.
    • Found a significant interaction between TGF-β pathway pPRS and red meat intake (ORint = 0.95, p = 0.003).
    • Specific variants (rs2337113 in SMAD7, rs2208603 near BMP5) within the TGF-β pathway showed significant interaction with red meat intake.

    Conclusions:

    • A statistically significant interaction exists between genetic variants in the TGF-β pathway and red meat consumption impacting CRC risk.
    • These findings provide mechanistic insights into the link between red meat intake and colorectal cancer development.