ArticleJCI insight2023
High-fat diet plus HNF1A variant promotes polyps by activating β-catenin in early-onset colorectal cancer.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Modifiable lifestyle and metabolic risk factors for colorectal polyps: a systematic review and meta-analysis.Frontiers in public health · 2025Pooled it
- Defective HNF1A hinders GLI3 processing favoring duodenal versus pancreatic fate, thus leading to intestinal elongation in vivo.Genes & development · 2026Article
- Metabolomics assisted by transcriptomics analysis to reveal metabolic characteristics and potential biomarkers of early-onset colorectal cancer.Discover oncology · 2026Article
- Why Is Colorectal Cancer Occurring Earlier? Metabolic Dysfunction, Underrecognized Carcinogens, and Emerging Controversies.Current obesity reports · 2026Review
- Recent advances in the design and development of small-molecule MMP-2 inhibitors.Future medicinal chemistry · 2025Review
- Early-onset colorectal cancer as an emerging disease of metabolic dysregulation.Nature reviews. Endocrinology · 2025Review
- Lipid metabolic reprogramming in colorectal cancer: Insights to mechanisms and therapeutics.World journal of gastrointestinal oncology · 2025Review
- Murine Models of Obesity-Related Cancer Risk.Cancer prevention research (Philadelphia, Pa.) · 2025Review
- Early Onset Colorectal Cancer: Molecular Underpinnings Accelerating Occurrence.Cellular and molecular gastroenterology and hepatology · 2025Review
- Conversational AI agent for precision oncology: AI-HOPE-WNT integrates clinical and genomic data to investigate WNT pathway dysregulation in colorectal cancer.Frontiers in artificial intelligence · 2025Article
- The Complex Role of Matrix Metalloproteinase-2 (MMP-2) in Health and Disease.International journal of molecular sciences · 2024Review
- Birth Cohort Colorectal Cancer (CRC): Implications for Research and Practice.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2024Review
- Direct and indirect effects of estrogens, androgens and intestinal microbiota on colorectal cancer.Frontiers in cellular and infection microbiology · 2024Review
- Obesity and early-onset colorectal cancer risk: emerging clinical evidence and biological mechanisms.Frontiers in oncology · 2024Review
- Review
- Trends and Projections of Early-Onset Colorectal Cancer Burden in China, 1990-2036: Findings From the Global Burden of Disease 2021 Study.Cancer control : journal of the Moffitt Cancer CenterArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
The incidence of early-onset colorectal cancer (EO-CRC) is rising and is poorly understood. Lifestyle factors and altered genetic background possibly contribute. Here, we performed targeted exon sequencing of archived leukocyte DNA from 158 EO-CRC participants, which identified a missense mutation at p.A98V within the proximal DNA binding domain of Hepatic Nuclear Factor 1 α (HNF1AA98V, rs1800574). The HNF1AA98V exhibited reduced DNA binding. To test function, the HNF1A variant was introduced into the mouse genome by CRISPR/Cas9, and the mice were placed on either a high-fat diet (HFD) or high-sugar diet (HSD). Only 1% of the HNF1A mutant mice developed polyps on normal chow; however, 19% and 3% developed polyps on the HFD and HSD, respectively. RNA-Seq revealed an increase in metabolic, immune, lipid biogenesis genes, and Wnt/β-catenin signaling components in the HNF1A mutant relative to the WT mice. Mouse polyps and colon cancers from participants carrying the HNF1AA98V variant exhibited reduced CDX2 and elevated β-catenin proteins. We further demonstrated decreased occupancy of HNF1AA98V at the Cdx2 locus and reduced Cdx2 promoter activity compared with WT HNF1A. Collectively, our study shows that the HNF1AA98V variant plus a HFD promotes the formation of colonic polyps by activating β-catenin via decreasing Cdx2 expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.