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Annals of Oncology Advance Access published online on April 13, 2005
Annals of Oncology, doi:10.1093/annonc/mdi189
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© 2005 European Society for Medical Oncology
Received November 23, 2004
Accepted January 24, 2005

Original article

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

M.-C. Etienne-Grimaldi 1, S. Pereira 2, N. Magné 3, J.-L. Formento 1, M. Francoual 1, X. Fontana 4, F. Demard 5, O. Dassonville 5, G. Poissonnet 5, J. Santini 6, R.-J. Bensadoun 7, P. Szepetowski 2, and G. Milano 1*

1 Laboratoire d'Oncopharmacologie, Centre Antoine Lacassagne, Nice, France
2 INSERM U491, Faculté de Médecine de la Timone, Marseille, France
3 Service de Radiothérapie, Institut Jules Bordet, Bruxelles, Belgique
4 Service de Médecine Nucléaire, Centre Antoine Lacassagne, Nice, France
5 Service ORL, Centre Antoine Lacassagne, Nice, France
6 Service ORL du CHU de Nice, Nice, France
7 Service de radiothérapie, Centre Antoine Lacassagne, Nice, France

* To whom correspondence should be addressed.
G. Milano, E-mail: gerard.milano{at}nice.fnclcc.fr


  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 ≥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.

Keywords: epidermal growth factor receptor; gene polymorphism; head and neck cancer; prognostic markers.

M.-C. Etienne-Grimaldi and S. Pereira contributed equally to this work.


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