Analysis of the dinucleotide repeat polymorphism in the epidermal growth factor receptor (EGFR) gene in head and neck cancer patients

Ann Oncol. 2005 Jun;16(6):934-41. doi: 10.1093/annonc/mdi189. Epub 2005 Apr 13.

Abstract

Background: Epidermal growth factor receptor (EGFR) overexpression is associated with poor prognosis in head and neck cancer. The first intron of EGFR gene is polymorphic (9-23 CA repeats) and transcription declines when the number of repeats increases.

Patients and methods: EGFR polymorphism (fluorescent genotyping) and expression (ligand-binding assay) were analyzed in tumors and normal tissues from 112 patients (100 men, 12 women; mean age 60 years).

Results: The number of CA repeats varied from 15 to 22. Allelic distribution was trimodal (predominance of 16, 20 and 18 CA repeats). EGFR concentrations were significantly higher (P=0.02) in homozygous tumors as compared with heterozygous. Considering homozygous tumors, or classifying genotypes as short/long/intermediary (two alleles <17 versus two alleles > or =17 versus others), no relationship was observed between tumoral EGFR genotype and expression. In the 76 tumors exhibiting at least one 16-CA allele, the length of the remaining allele was inversely correlated to EGFR expression (P=0.047). Tumoral EGFR expression, performance status (WHO criteria) and node involvement were independent predictors of specific survival (P <0.01). Tumoral or normal tissue EGFR genotype did not influence survival.

Conclusions: Intron 1 EGFR polymorphism may be implicated in the regulation of EGFR expression in head and neck tumors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dinucleotide Repeats*
  • ErbB Receptors / genetics*
  • Female
  • Genotype
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / mortality
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*

Substances

  • ErbB Receptors