ArticleCarcinogenesis2016
FGFR2 risk SNPs confer breast cancer risk by augmenting oestrogen responsiveness.
Article in Carcinogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
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- Isoform-specific single-cell perturb-seq reveals distinct functions of alternative promoters in drug response.Nucleic acids research · 2026Article
- Reconstruction of the transcriptional regulatory networks in the kidney of desert-adapted species.Communications biology · 2025Article
- PIT-1/SF-1-positive pituitary tumors in patients with acromegaly: transcriptomic perspective.Acta neuropathologica communications · 2025Article
- Illuminating the Noncoding Genome in Cancer Using Artificial Intelligence.Cancer research · 2025Review
- Potential Influence ofInternational journal of molecular sciences · 2025Article
- LowerBiology · 2024Article
- Revolutionizing Pathology with Artificial Intelligence: Innovations in Immunohistochemistry.Journal of personalized medicine · 2024Review
- Prognostic value ofContemporary oncology (Poznan, Poland) · 2024Article
- Genetic variants of ADAM9 as potential predictors for biochemical recurrence in prostate cancer patients after receiving a radical prostatectomy.International journal of medical sciences · 2024Article
- FGFR2 genetic variants in women with breast cancer.Molecular medicine reports · 2023Article
- Review
- Genetic variants of dipeptidyl peptidase IV are linked to the clinicopathologic development of prostate cancer.Journal of cellular and molecular medicine · 2023Article
- Identification of non-coding silencer elements and their regulation of gene expression.Nature reviews. Molecular cell biology · 2023Review
- FGFR2 Controls Growth, Adhesion and Migration of Nontumorigenic Human Mammary Epithelial Cells by Regulation of Integrin β1 Degradation.Journal of mammary gland biology and neoplasia · 2023Article
- Transcriptional Profile of Human Pancreatic Acinar Ductal Metaplasia.Gastro hep advances · 2023Article
- CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states.Nature neuroscience · 2022Article
- FGF7/FGFR2-JunB signalling counteracts the effect of progesterone in luminal breast cancer.Molecular oncology · 2022Article
- The genomic and transcriptome characteristics of lung adenocarcinoma patients with previous breast cancer.BMC cancer · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
The fibroblast growth factor receptor 2 (FGFR2) locus is consistently the top hit in genome-wide association studies for oestrogen receptor-positive (ER(+)) breast cancer. Yet, its mode of action continues to be controversial. Here, we employ a systems biology approach to demonstrate that signalling via FGFR2 counteracts cell activation by oestrogen. In the presence of oestrogen, the oestrogen receptor (ESR1) regulon (set of ESR1 target genes) is in an active state. However, signalling by FGFR2 is able to reverse the activity of the ESR1 regulon. This effect is seen in multiple distinct FGFR2 signalling model systems, across multiple cells lines and is dependent on the presence of FGFR2. Increased oestrogen exposure has long been associated with an increased risk of breast cancer. We therefore hypothesized that risk variants should reduce FGFR2 expression and subsequent signalling. Indeed, transient transfection experiments assaying the three independent variants of the FGFR2 risk locus (rs2981578, rs35054928 and rs45631563) in their normal chromosomal context show that these single-nucleotide polymorphisms (SNPs) map to transcriptional silencer elements and that, compared with wild type, the risk alleles augment silencer activity. The presence of risk variants results in lower FGFR2 expression and increased oestrogen responsiveness. We thus propose a molecular mechanism by which FGFR2 can confer increased breast cancer risk that is consistent with oestrogen exposure as a major driver of breast cancer risk. Our findings may have implications for the clinical use of FGFR2 inhibitors.
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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.