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
Joel Sanchez Mendez, Bryan Queme, Yubo Fu, John L. Morrison, Juan Pablo Lewinger, Eric S. Kawaguchi, Huaiyu Mi, Mireia Obón‐Santacana et al.. Cancer Epidemiology Biomarkers & Prevention, 2026-04-01
Topic: Brain proteins, microglia and lab models
A total of 30 variants were overrepresented in four pathways: presenilin/Alzheimer disease, cadherin/WNT signaling, gonadotropin-releasing hormone receptor, and transforming growth factor-β (TGF-β) signaling. We found a significant interaction between TGF-β pPRS and red meat intake [ORint = 0.95; 95% confidence interval (CI) = 0.92-0.98; P = 0.003). When variants in the TGF-β pathway were assessed, we observed significant interactions of red meat with rs2337113 [intron SMAD family member 7 (SMAD7) gene, Chr18] and rs2208603 [intergenic region bone morphogenetic protein 5 (BMP5), Chr6; P = 0.0005 and 0.036, respectively]. There was no evidence of pPRS × red meat interactions for other pathways or with processed meat. This pathway-based interaction analysis revealed a statistically significant interaction between variants in the TGF-β pathway and red meat consumption that influences colorectal cancer risk. IMPACT: These findings shed light on the possible mechanistic link between red meat consumption and colorectal cancer risk.
Key findings
- A total of 30 variants were overrepresented in four pathways: presenilin/Alzheimer disease, cadherin/WNT signaling, gonadotropin-releasing hormone receptor, and transforming growth factor-β (TGF-β) signaling.
- We found a significant interaction between TGF-β pPRS and red meat intake [ORint = 0.95; 95% confidence interval (CI) = 0.92-0.98; P = 0.003).
- When variants in the TGF-β pathway were assessed, we observed significant interactions of red meat with rs2337113 [intron SMAD family member 7 (SMAD7) gene, Chr18] and rs2208603 [intergenic region bone morphogenetic protein 5 (BMP5), Chr6; P = 0.0005 and 0.036, respectively].
- There was no evidence of pPRS × red meat interactions for other pathways or with processed meat.
- This pathway-based interaction analysis revealed a statistically significant interaction between variants in the TGF-β pathway and red meat consumption that influences colorectal cancer risk.
Why it matters
This study is about colorectal cancer risk and found an interaction between TGF-β pathway variants and red meat intake; an Alzheimer disease pathway appeared only among the pathways analyzed. It reports no treatment, cure, or prevention findings for Alzheimer disease.
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Study details
- Participants204
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cancer Epidemiology Biomarkers & Prevention) |
| Journal's citation record | 2 / 4 | Cancer Epidemiology Biomarkers & Prevention: journal h-index 210 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 204 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author W. James Gauderman: h-index 75 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 44 institution(s) in 12 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41920173) |
| Free to read | 2 / 2 | Free to read |
| Total | 47 / 100 | — |
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Read the original
- DOI: 10.1158/1055-9965.epi-25-1754
- PubMed: 41920173
- Original source →
- Free full text: Socio-Environmental Systems Modeling →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Mendez, J. S., Queme, B., Fu, Y., Morrison, J. L., Lewinger, J. P., Kawaguchi, E. S., et al. (2026). 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. Cancer Epidemiology Biomarkers & Prevention. https://doi.org/10.1158/1055-9965.epi-25-1754
Vancouver
Mendez JS, Queme B, Fu Y, Morrison JL, Lewinger JP, Kawaguchi ES, et al. 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. Cancer Epidemiology Biomarkers & Prevention. 2026. doi:10.1158/1055-9965.epi-25-1754. PMID: 41920173.
BibTeX
@article{mendez2026-41920173,
author = {Mendez, Joel Sanchez and Queme, Bryan and Fu, Yubo and Morrison, John L. and Lewinger, Juan Pablo and Kawaguchi, Eric S. and Mi, Huaiyu and Obón‐Santacana, Mireia and others},
title = {{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}},
journal = {Cancer Epidemiology Biomarkers \& Prevention},
year = {2026},
doi = {10.1158/1055-9965.epi-25-1754},
pmid = {41920173},
url = {https://doi.org/10.1158/1055-9965.epi-25-1754}
}