Epidermal growth factor receptor (EGFR) gene overexpression has been implicated in the development of many types of tumors, including glioblastomas, the most frequent diffusely infiltrating astrocytomas. However, little is known about the influence of the polymorphisms of EGFR on EGFR production and/or activity, possibly modulating the susceptibility to astrocytomas. This study aimed to examine the association of two EGFR promoter polymorphisms (c-191C>A and c.-216G>T) and the c.2073A>T polymorphism located in exon 16 with susceptibility to astrocytomas, EGFR gene expression and survival in a case-control study of 193 astrocytoma patients and 200 cancer-free controls. We found that the variant TT genotype of the EGFR c.2073A>T polymorphism was associated with a significantly decreased risk of astrocytoma when compared with the AA genotype [sex- and age-adjusted odds ratio 0.51, 95% confidence interval 0.26–0.98]. No association of the two promoter EGFR polymorphisms (or combinations of these polymorphisms) and risk of astrocytomas, EGFR expression or survival was found. Our findings suggest that modulation of the EGFR c.2073A>T polymorphism could play a role in future therapeutic approaches to astrocytoma.
WrenschM., MinnY., ChewT., BondyM., BergerM.S.. Epidemiology of primary brain tumors: current concepts and review of the literature.Neuro Oncol2002; 4: 278–99.
3.
LouisD.N., OhgakiH., WiestlerO.D., CaveneeW.K., eds. Pathology and genetics of tumours of the nervous system,4th ed.Lyon, France: IARC/WHO Press, 2007.
4.
LouisD.N., OhgakiH., WiestlerO.D.. The 2007 WHO classification of tumours of the central nervous system.Acta Neuropathol2007; 114: 97–109.
5.
KorshunovA., SychevaR., GolanovA.. The prognostic relevance of molecular alterations in glioblastomas for patients age < 50 years.Cancer2005; 104: 825–32.
6.
WatanabeK., TachibanaO., SataK., YonekawaY., KleihuesP., OhgakiH.. Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas.Brain Pathol1996; 6: 217–23.
7.
UnoM., Oba-ShinjoS.M., WakamatsuA.. Association of TP53 mutation, p53 overexpression, and p53 codon 72 polymorphism with susceptibility to apoptosis in adult patients with diffuse astrocytomas.Int J Biol Markers2006; 21: 50–7.
8.
UnoM., Oba-ShinjoS.M., de AguiarP.H.. Detection of somatic TP53 splice site mutations in diffuse astrocytomas.Cancer Lett2005; 224: 321–7.
9.
KumarA., PetriE.T., HalmosB., BoggonT.J.. Structure and clinical relevance of the epidermal growth factor receptor in human cancer.J Clin Oncol2008; 26: 1742–51.
Belda-IniestaC., de Castro CarpeñoJ., Casado SáenzE., Cejas GuerreroP., PeronaR., González BarónM.. Molecular biology of malignant gliomas.Clin Transl Oncol2006; 8: 635–41.
12.
Belda-IniestaC., de Castro CarpeñoJ., SerenoM., González-BarónM., PeronaR.. Epidermal growth factor receptor and glioblastoma multiforme: molecular basis for a new approach.Clin Transl Oncol2008; 10: 73–7.
13.
ShinojimaN., TadaK., ShiraishiS.. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme.Cancer Res2003; 63: 6962–70.
14.
LiuW., InnocentiF., WuM.H.. A functional common polymorphism in a Sp1 recognition site of the epidermal growth factor receptor gene promoter.Cancer Res2005; 65: 46–53.
15.
CarpentierC., Laigle-DonadeyF., MarieY.. Polymorphism in Sp1 recognition site of the EGF receptor gene promoter and risk of glioblastoma.Neurology2006; 67: 872–4.
16.
NomuraM., ShigematsuH., LiL.. Polymorphisms, mutations, and amplification of the EGFR gene in non-small cell lung cancers.PLoS Med2007; 4: e125.
17.
SpindlerK.L., NielsenJ.N., LindebjergJ., BrandslundI., JakobsenA.. Prediction of response to chemoradiation in rectal cancer by a gene polymorphism in the epidermal growth factor receptor promoter region.Int J Radiat Oncol Biol Phys2006; 66: 500–4.
18.
LiuG., GurubhagavatulaS., ZhouW.. Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib.Pharmacogenomics J2008; 8: 129–38.
19.
GregorcV., HidalgoM., SpreaficoA.. Germline polymorphisms in EGFR and survival in patients with lung cancer receiving gefitinib.Clin Pharmacol Ther2008; 83: 477–84.
20.
HsiehY.Y., ChangC.C., TsaiF.J., LinC.C., TsaiC.H.. T homozygote and allele of epidermal growth factor receptor 2073 gene polymorphism are associated with higher susceptibility to endometriosis and leiomyomas.Fertil Steril2005; 83: 796–9.
21.
ShintaniS., MatsuoK., CrohinC.C.. Intragenic mutation analysis of the human epidermal growth factor receptor (EGFR) gene in malignant human oral keratinocytes.Cancer Res1999; 59: 4142–7.
22.
KitaoK., YoshidaS., KennedyS.. Epidermal growth factor receptor and human epidermal growth factor receptor 2 gene polymorphisms in endometrial cancer in a Japanese population.Reprod Sci2007; 14: 349–56.
23.
InagakiM., YoshidaS., KennedyS.. Association study between epidermal growth factor receptor and epidermal growth factor polymorphisms and endometriosis in a Japanese population.Gynecol Endocrinol2007; 23: 1–5.
24.
VoelzkeW.R., PettyW.J., LesserG.J.. Targeting the epidermal growth factor receptor in high-grade astrocytomas.Curr Treat Options Oncol2008; 9: 23–31.
25.
MillerS.A., DykesD.D., PoleskyH.F.. A simple salting out procedure for extracting DNA from human nucleated cells.Nucleic Acids Res1988; 16: 1215.
26.
Oba-ShinjoS.M., BengtsonM.H., WinnischoferS.M.. Identification of novel differentially expressed genes in human astrocytomas by cDNA representational difference analysis.Mol Brain Res2005; 140: 25–33.
27.
LivakK.J., SchmittgenT.D.. Analysis of relative gene expression data using real-time quantitative PCR and the 2-AACt method.Methods2001; 25: 402–8.
28.
LiuW., WuX., ZhangW.. Relationship of EGFR mutations, expression, amplification, and polymorphisms to epidermal growth factor receptor inhibitors in the NCI60 cell lines.Clin Cancer Res2007; 13: 6788–95.
29.
BandrésE., BarricarteR., CanteroC.. Epidermal growth factor receptor (EGFR) polymorphism and survival in head and neck cancer patients.Oral Oncol2007; 43: 713–9.
