Polymorphism in epidermal growth factor receptor intron 1 predicts prognosis of patients with esophageal cancer after chemoradiation and surgery

Ann Surg Oncol. 2011 Jul;18(7):2066-73. doi: 10.1245/s10434-011-1559-9. Epub 2011 Feb 5.

Abstract

Background: The EGFR gene has been demonstrated to be an important factor influencing treatment response for various cancers, and its expression has been shown to be modified by the polymorphic CA repeat length at the 5'-regulatory sequence in intron 1. We investigated whether this EGFR polymorphism is associated with prognosis in patients with esophageal cancer after concurrent chemoradiotherapy (CCRT) and esophagectomy.

Methods: A cohort of 148 patients with esophageal cancer received cisplatin-based CCRT (concurrently combined with 40 Gy irradiation) and subsequent esophagectomy. Their EGFR genotypes were determined by polymerase chain reaction from leukocyte DNA, which was obtained before treatment and was correlated with patient survival.

Results: Patients with the homozygous short allele (<20 CA) of the EGFR gene in intron 1 were more likely to have a shorter duration of survival after CCRT and surgery than those with the homozygous long allele [adjusted hazard ratio (HR) (95% confidence interval [CI]) of death: 1.88 (1.02-3.49); P = 0.045]. This unfavorable prognostic effect of EGFR homozygous short CA repeat was mainly manifested in patients with good response to CCRT [adjusted HR (95% CI) of death 3.40 (1.06-10.89); P = 0.039]; it was less evident in those with poor response to CCRT [adjusted HR (95% CI) 1.40 (0.65-3.02); P = 0.384].

Conclusions: The EGFR CA repeat genetic polymorphism may act as a valuable molecular predictor of clinical outcome of esophageal cancer after CCRT and esophagectomy, especially in those with good response to CCRT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brachytherapy*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / therapy
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / genetics
  • ErbB Receptors / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy
  • Esophagectomy*
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Introns / genetics*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Paclitaxel / administration & dosage
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Survival Rate

Substances

  • DNA, Neoplasm
  • EGFR protein, human
  • ErbB Receptors
  • Paclitaxel
  • Cisplatin
  • Fluorouracil