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Epidermal growth factor receptor R497K polymorphism is a favorable prognostic factor for patients with colorectal

Wei-Shu Wang1, Po-Min Chen, Tzeon-Jye Chiou

  • 1National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 19, 2007
PubMed
Abstract

Insights

The R497K polymorphism in epidermal growth factor receptor (EGFR) is linked to better outcomes in colorectal cancer patients. This genetic variation is associated with reduced tumor recurrence and longer survival, offering potential prognostic value.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Epidermal growth factor receptor (EGFR) activation is linked to poor prognosis in colorectal carcinoma.
  • The R497K polymorphism of EGFR exhibits attenuated functions in ligand binding, kinase activation, and growth stimulation.

Purpose of the Study:

  • To investigate the influence of the R497K polymorphism of EGFR on the clinicopathologic features and prognosis of colorectal carcinoma patients.
  • To assess the R497K polymorphism as a potential prognostic factor in colorectal cancer.

Main Methods:

  • Retrospective analysis of 209 colorectal carcinoma patients (100 with stage II/III, 109 with metastatic disease).
  • Evaluation of R497K polymorphism in white blood cells and tumor tissues.
  • Assessment of EGFR phosphorylation, c-Myc activation, and correlation with clinicopathologic features and survival outcomes.

Main Results:

  • R497K polymorphism showed no significant difference between patients with or without colorectal carcinoma.
  • In stage II/III patients receiving curative surgery, R497K was associated with decreased EGFR phosphorylation, c-Myc activation, reduced invasion, lower nodal involvement, less metastasis, and improved disease-free and overall survival.
  • In metastatic patients, R497K was linked to better response to 5-fluorouracil/oxaliplatin and longer survival.
  • Multivariate analysis identified R497K as an independent prognostic factor.

Conclusions:

  • The R497K polymorphism of EGFR, by reducing its activation, may be a key determinant for reduced tumor recurrence in stage II/III colorectal carcinoma patients.
  • This polymorphism is associated with longer survival in both stage II/III and metastatic colorectal carcinoma patients.
  • EGFR R497K polymorphism offers potential as a predictive biomarker for treatment response and prognosis in colorectal cancer.

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