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


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.
Etienne-Grimaldi
M-C
MC
Laboratoire d'Oncopharmacologie, Centre Antoine Lacassagne, Nice, France.
Pereira
S
S
Magné
N
N
Formento
J-L
JL
Francoual
M
M
Fontana
X
X
Demard
F
F
Dassonville
O
O
Poissonnet
G
G
Santini
J
J
Bensadoun
R-J
RJ
Szepetowski
P
P
Milano
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018900:Dinucleotide Repeats; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic
D066246:ErbB Receptors