title: Investigation of ICAM-1 and β3 integrin gene variations in patients with brain tumors.
abstract: BACKGROUND
  Primary brain tumors constitute a small percent of all malignant cancers, but their etiology remains poorly understood. β3 integrin (ITGB3) has been recognized to play influential roles in angiogenesis, tumor growth and metastasis. Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and ITGB3 could be associated with brain cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between brain tumor risk and ICAM-1 and β3 integrin gene polymorphisms.
  
  
  METHODS
  The study covered 92 patients with primary brain tumors and 92 age-matched healthy control subjects. Evaluation of β3 integrin (Leu33Pro (rs5918)) and ICAM-1 (R241G (rs1799969) and K469E (rs5498)) gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
  
  
  RESULTS
  According to results of our research, the A allele of the ICAM-1 R241G gene polymorphism appeared to be a risk factor for primary brain tumors (p<0.001). Similarly, the frequency of the A mutant allele of ICAM-1 R241G was statistically significant in patients with brain tumors classified as glioma (p<0.001). When allele and genotype distributions of ICAM- 1 K469E, ICAM-1 R241G and β3 integrin Leu33Pro gene polymorphisms were evaluated with age, sex, and smoking, there were no statistically significant differences. Haplotype analysis revealed that the frequencies of GAC (rs1799969-rs5498-rs5918) and GAT (rs1799969-rs5498-rs5918) haplotypes were significantly lower in patients as compared with controls (p=0.001; p=0.036 respectively).
  
  
  CONCLUSIONS
  This study provides the first evidence that ICAM-1 R241G SNP significantly contributes to the risk of primary brain tumors in a Turkish population. In addition, our results suggest that ICAM-1 R241G in combination ICAM-1 K469E may have protective effects against the development of brain cancer.
authors.affiliation: Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey E-mail : umz67@yahoo.com.
authors.forename: Umit
authors.initials: U
authors.lastname: Yilmaz
authors.forename: Umit
authors.initials: U
authors.lastname: Zeybek
authors.forename: Ozlem Timirci
authors.initials: OT
authors.lastname: Kahraman
authors.forename: Ali Metin
authors.initials: AM
authors.lastname: Kafadar
authors.forename: Bahar
authors.initials: B
authors.lastname: Toptas
authors.forename: Nesibe
authors.initials: N
authors.lastname: Yamak
authors.forename: Faruk
authors.initials: F
authors.lastname: Celik
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylim
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C061248:ITGB3 protein, human; D039661:Integrin beta3; D018799:Intercellular Adhesion Molecule-1; D004247:DNA