title: Distribution and Effects of CDKN2 p16 540 C>G and 580 C>T, and MDM2 SNP309 T>G Polymorphisms in Patients with Primary Brain Tumors.
abstract: OBJECTIVE
  Primary brain tumors are unique tumors due to their different pathobiological behavior, while they rarely metastasize outside the central nervous system. Regarding the oncogenesis of primary brain tumors, it was shown that changes in functions of p16 and mouse double minute 2 homolog (MDM2) are related to tumor pathogenesis by enhancing cell proliferation and malign development. The present study aims to evaluate the possible associations between cyclin-dependent kinase 2 (CDKN2) p16 540 C>G and 580 C>T, MDM2 single nucleotide polymorphism 309 (SNP309) T>G polymorphisms and primary brain tumor.
  
  
  METHODS
  Using polymerase chain reaction-restriction fragment length polymorphism technique, we determined SNPs in 67 patients with primary brain tumors and 71 healthy volunteers without malignancy.
  
  
  RESULTS
  The frequency of CC genotype for CDKN2 p16 540 C>G was significantly two-fold higher (p<0.001) and possessing a C allele conferred a ~7-fold increased risk (p=0.005) of primary brain tumor. We also found that the CC genotype produced a higher ~4-fold risk of glioma (p=0.001) and the G allele had a possibly protective role against meningioma (~4.8-fold reduced risk, p=0.001). We found no significant associations for CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants between cases and controls. CGT haplotype was significantly less frequent in patients with primary brain tumors and glioma cases (p=0.009 and p=0.028, respectively) than controls. CGG haplotype was significantly less frequent in patients with meningioma versus the control group (p=0.023).
  
  
  CONCLUSIONS
  These findings show that CDKN2 p16 540 C>G, CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants and their haplotypes may be risk factors for the development of primary brain tumors, especially of glioma.
authors.affiliation: Department of Neurosurgery, Cerrahpasa Medical Faculty, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey ctfkafadar@gmail.com ilhanyaylim@gmail.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Kafadar
authors.affiliation: Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Küçükhüseyin
authors.affiliation: Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Saime
authors.initials: S
authors.lastname: Turan
authors.affiliation: Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ezgi Nurdan
authors.initials: EN
authors.lastname: Yenilmez
authors.affiliation: Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Servet
authors.initials: S
authors.lastname: Tunoglu
authors.affiliation: Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Umit
authors.initials: U
authors.lastname: Zeybek
authors.affiliation: Department of Neurosurgery, Cerrahpasa Medical Faculty, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Mehmet Yasar
authors.initials: MY
authors.lastname: Kaynar
authors.affiliation: Department of Neurosurgery, Cerrahpasa Medical Faculty, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Rahsan
authors.initials: R
authors.lastname: Kemerdere
authors.affiliation: Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey ctfkafadar@gmail.com ilhanyaylim@gmail.com.
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylim
mesh_terms: D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005910:Glioma / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008579:Meningioma / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012306:Risk
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Brain tumor; MDM2; glioma; meningioma; p16; polymorphism