ArticlePLoS biology2008
Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer.
Article in PLoS biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 279 citations in OpenAlex.
- Correlation of FGFR2 rs2981582 polymorphisms with susceptibility to breast cancer: a case-control study in a Chinese population.The Journal of international medical research · 2019Pooled it
- A phase II, open-label study of ramucirumab in combination with paclitaxel and carboplatin as first-line therapy in patients with stage IIIB/IV non-small-cell lung cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2014Trial
- Variation in the FGFR2 gene and the effect of a low-fat dietary pattern on invasive breast cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2010Trial
- Variation in the FGFR2 gene and the effects of postmenopausal hormone therapy on invasive breast cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2009Trial
- Article
- Breast Cancer Progression by the FGF/FGFR Axis: A Metabolic Perspective.Journal of mammary gland biology and neoplasia · 2025Review
- Maternal histone methyltransferases antagonistically regulate autosomal random monoallelic expression (aRMAE) in C. elegans.Nature communications · 2025Article
- Article
- Understanding genetic variations associated with familial breast cancer.World journal of surgical oncology · 2024Review
- Identification of candidate causal variants and target genes at 41 breast cancer risk loci through differential allelic expression analysis.Scientific reports · 2024Article
- FGFR2 genetic variants in women with breast cancer.Molecular medicine reports · 2023Article
- A Functional Variant Alters the Binding ofAnimals : an open access journal from MDPI · 2023Article
- Refining the genetic risk of breast cancer with rare haplotypes and pattern mining.Life science alliance · 2023Article
- Evaluation of the Association betweenGenes · 2023Article
- COL1A1 and FGFR2 Single-Nucleotide Polymorphisms Found in Class II and Class III Skeletal Malocclusions in Javanese Population.European journal of dentistry · 2023Article
- Predicting the effects of rare genetic variants on oncogenic signaling pathways: A computational analysis of HRAS protein function.Frontiers in chemistry · 2023Article
- Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant.NPJ breast cancer · 2022Article
- Allelic imbalance of chromatin accessibility in cancer identifies candidate causal risk variants and their mechanisms.Nature genetics · 2022Article
- Functional annotation of breast cancer risk loci: current progress and future directions.British journal of cancer · 2022Review
- Exploring the effects of genetic variation on gene regulation in cancer in the context of 3D genome structure.BMC genomic data · 2022Article
101 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The recent whole-genome scan for breast cancer has revealed the FGFR2 (fibroblast growth factor receptor 2) gene as a locus associated with a small, but highly significant, increase in the risk of developing breast cancer. Using fine-scale genetic mapping of the region, it has been possible to narrow the causative locus to a haplotype of eight strongly linked single nucleotide polymorphisms (SNPs) spanning a region of 7.5 kilobases (kb) in the second intron of the FGFR2 gene. Here we describe a functional analysis to define the causative SNP, and we propose a model for a disease mechanism. Using gene expression microarray data, we observed a trend of increased FGFR2 expression in the rare homozygotes. This trend was confirmed using real-time (RT) PCR, with the difference between the rare and the common homozygotes yielding a Wilcox p-value of 0.028. To elucidate which SNPs might be responsible for this difference, we examined protein-DNA interactions for the eight most strongly disease-associated SNPs in different breast cell lines. We identify two cis-regulatory SNPs that alter binding affinity for transcription factors Oct-1/Runx2 and C/EBPbeta, and we demonstrate that both sites are occupied in vivo. In transient transfection experiments, the two SNPs can synergize giving rise to increased FGFR2 expression. We propose a model in which the Oct-1/Runx2 and C/EBPbeta binding sites in the disease-associated allele are able to lead to an increase in FGFR2 gene expression, thereby increasing the propensity for tumour formation.
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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.