ArticleCancer science2012
Epidermal growth factor receptor R521K polymorphism shows favorable outcomes in KRAS wild-type colorectal cancer patients treated with cetuximab-based chemotherapy.
Article in Cancer science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis.The pharmacogenomics journal · 2017Pooled it
- Two independent variants of epidermal growth factor receptor associated with risk of glioma in a Korean population.Scientific reports · 2022Article
- The Investigation of Associations betweenDiagnostics (Basel, Switzerland) · 2021Article
- Polymorphisms inInternational journal of molecular sciences · 2021Article
- Genetic variants of the EGFR ligand-binding domain and their association with structural alterations in Arab cancer patients.BMC research notes · 2021Article
- Association between polymorphisms in EGFR and tumor response during cetuximab and oxaliplatin-based combination therapy in metastatic colorectal cancer: Analysis of data from two clinical trials.Oncology letters · 2019Article
- Single Amino Acid Variant Discovery in Small Numbers of Cells.Journal of proteome research · 2019Article
- Tyrosine kinase domain mutations ofOncoTargets and therapy · 2017Article
- Evaluation of the EGFR polymorphism R497K in two cohorts of neoadjuvantly treated breast cancer patients.PloS one · 2017Article
- Simul-seq: combined DNA and RNA sequencing for whole-genome and transcriptome profiling.Nature methods · 2016Article
- PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response.The Journal of clinical investigation · 2015Article
- EGFR ligands and DNA repair genes: genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer.The pharmacogenomics journal · 2015Article
- ErbB polymorphisms: insights and implications for response to targeted cancer therapeutics.Frontiers in genetics · 2015Review
- FcγR and EGFR polymorphisms as predictive markers of cetuximab efficacy in metastatic colorectal cancer.Molecular diagnosis & therapy · 2014Article
- Intergenic polymorphisms in the amphiregulin gene region as biomarkers in metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan.The pharmacogenomics journal · 2014Article
- EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy.OncoTargets and therapy · 2014Article
- A Meta-Analysis on the Relations between EGFR R521K Polymorphism and Risk of Cancer.International journal of genomics · 2014Article
- A patient-derived somatic mutation in the epidermal growth factor receptor ligand-binding domain confers increased sensitivity to cetuximab in head and neck cancer.European journal of cancer (Oxford, England : 1990) · 2013Article
- Allele Frequencies of the Epidermal Growth Factor Receptors Polymorphism R521K in Colorectal Cancer Patients and Healthy Subjects Indicate a Risk-Reducing Effect of K521 in Syrian Population.North American journal of medical sciences · 2013Article
- Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The R521K polymorphism of epidermal growth factor receptor has attenuated affinity in ligand binding and proto-oncogene induction, which may affect the efficacy of cetuximab. We analyzed the effect of this polymorphism on the outcome of 112 patients with KRAS wild-type metastatic colorectal carcinoma treated with first-line cetuximab plus FOLFOX-4. The associations of this polymorphism with vascular endothelial growth factor (VEGF) expression and clinicopathologic characteristics were also examined. The results showed that the frequencies of the G/G, G/A, and A/A genotypes were 32.1% (n = 36), 42.9% (n = 48), and 25.0% (n = 28), respectively. A marked decrease in VEGF expression levels (66.7% vs 28.9%, P < 0.01) was observed in patients with 521A allele variants (Arg/Lys or Lys/Lys), which were associated with a decreased tumor size (55.6% vs 31.6%, P = 0.02), good histological differentiation (63.9% vs 85.5%, P = 0.01), decreased lymphovascular invasion (69.4% vs 39.5%, P < 0.01), and a higher response rate to cetuximab plus FOLFOX treatment (55.6% vs 78.9%, P = 0.01). In addition, this polymorphism was associated with a longer progression-free period (P = 0.001) and overall survival (P = 0.001). By multivariate analysis, this polymorphism was also identified as an independent prognostic factor. These data suggest that the R521K polymorphism of epidermal growth factor receptor, by reducing its activation and a consequential downregulation of its target genes, including VEGF, could be a key determinant of an increased response to cetuximab-based chemotherapy and a longer survival for KRAS wild-type colorectal carcinoma patients.
Indexed as
Identifiers
What OpenQuestion holds
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.