ArticleCell reports2014
A polymorphic enhancer near GREM1 influences bowel cancer risk through differential CDX2 and TCF7L2 binding.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Five endometrial cancer risk loci identified through genome-wide association analysis.Nature genetics · 2016Pooled it
- Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma.Nature communications · 2016Pooled it
- Genetic variants linked to type 2 diabetes in CDKN1B and TCF7L2 influence survival outcomes in metastatic colorectal cancer.International journal of cancer · 2025Article
- The Role of GREMLIN1, a Bone Morphogenetic Protein Antagonist, in Cancer Stem Cell Regulation.Cells · 2025Review
- Rapid and quantitative functional interrogation of human enhancer variant activity in live mice.Nature communications · 2025Article
- Rapid and Quantitative Functional Interrogation of Human Enhancer Variant Activity in Live Mice.bioRxiv : the preprint server for biology · 2023Article
- Association ofGenes · 2022Article
- Alterations to Genome Organisation in Stem Cells, Their Differentiation and Associated Diseases.Results and problems in cell differentiation · 2022Article
- LGR6 activates the Wnt/β-catenin signaling pathway and forms a β-catenin/TCF7L2/LGR6 feedback loop in LGR6Oncogene · 2021Article
- Wnt target enhancer regulation by a CDX/TCF transcription factor collective and a novel DNA motif.Nucleic acids research · 2021Article
- Non-Lynch Familial and Early-Onset Colorectal Cancer Explained by Accumulation of Low-Risk Genetic Variants.Cancers · 2021Article
- SNPs associated with colorectal cancer at 15q13.3 affect risk enhancers that modulate GREM1 gene expression.Human mutation · 2021Article
- Subversion of Niche-Signalling Pathways in Colorectal Cancer: What Makes and Breaks the Intestinal Stem Cell.Cancers · 2021Review
- Colorectal cancer genetic variants are also associated with serrated polyposis syndrome susceptibility.Journal of medical genetics · 2020Article
- No evidence of Gremlin1-mediated activation of VEGFR2 signaling in endothelial cells.The Journal of biological chemistry · 2019Article
- Association analyses identify 31 new risk loci for colorectal cancer susceptibility.Nature communications · 2019Article
- Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer.Human genetics · 2019Article
- Overexpression of mircoRNA-137 inhibits cervical cancer cell invasion, migration and epithelial-mesenchymal transition by suppressing the TGF-β/smad pathway via binding to GREM1.Cancer cell international · 2019Article
- A functional variant in GREM1 confers risk for colorectal cancer by disrupting a hsa-miR-185-3p binding site.Oncotarget · 2017Article
- Bone morphogenetic protein and Notch signalling crosstalk in poor-prognosis, mesenchymal-subtype colorectal cancer.The Journal of pathology · 2017Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 3 countries.
Funding
Abstract
A rare germline duplication upstream of the bone morphogenetic protein antagonist GREM1 causes a Mendelian-dominant predisposition to colorectal cancer (CRC). The underlying disease mechanism is strong, ectopic GREM1 overexpression in the intestinal epithelium. Here, we confirm that a common GREM1 polymorphism, rs16969681, is also associated with CRC susceptibility, conferring ∼20% differential risk in the general population. We hypothesized the underlying cause to be moderate differences in GREM1 expression. We showed that rs16969681 lies in a region of active chromatin with allele- and tissue-specific enhancer activity. The CRC high-risk allele was associated with stronger gene expression, and higher Grem1 mRNA levels increased the intestinal tumor burden in Apc(Min) mice. The intestine-specific transcription factor CDX2 and Wnt effector TCF7L2 bound near rs16969681, with significantly higher affinity for the risk allele, and CDX2 overexpression in CDX2/GREM1-negative cells caused re-expression of GREM1. rs16969681 influences CRC risk through effects on Wnt-driven GREM1 expression in colorectal tumors.
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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.