title: Polymorphic expression of glutathione transferases A1, M1, P1 and T1 in epithelial ovarian cancer: a Serbian case-control study.
abstract: OBJECTIVE
  Since several studies have proposed that epithelial ovarian cancer should not be considered as a single disease entity and that it results from an accumulation of genetic changes, we aimed to assess the polymorphic expression of major cytosolic glutathione S-transferases (GSTM1, T1, A1 and P1) with respect to ovarian cancer susceptibility and aggressiveness.
  
  
  METHODS
  This case-control study was conducted on 93 newly diagnosed epithelial ovarian cancer patients and 178 healthy matched controls. The multiplex polymerase chain reaction (PCR) was used to detect homozygous deletions of GSTM1 and GSTT1 genes. Analysis of the single nucleotide polymorphism (SNP) GSTA1 C69T was performed using PCR-restriction fragment length polymorphism (RFLP), while for SNP GSTP1 Ile105Val real-time PCR was used.
  
  
  RESULTS
  No significant association to ovarian cancer risk was found for individual GSTM1, GSTA1 and GSTP1 genotypes (p>0.05). However, the carriers of GSTT1-active genotype were at 2-fold higher risk of ovarian cancer development (95%CI: 1.00-4.01, p=0.049), which was even more elevated in the subgroup of patients with positive family history of cancer. Moreover, the frequency of all three GST genotypes that might be associated to ovarian cancer risk (GSTT1-active, GSTA1-active and GSTP1-referent) was significantly higher in patients than in the control group (p=0.042). Even more, patients who were carriers of combination of these three genotypes represented over 64% of the total number of patients within any of the International Federation of Gynecology and Obstetrics (FIGO) stages of ovarian cancer.
  
  
  CONCLUSIONS
  This study provides supportive evidence that GSTs might affect both susceptibility and progression of ovarian cancer.
authors.affiliation: Clinic of Gynecology, University Teaching Hospital Zemun-Belgrade, Serbia.
authors.forename: Igor
authors.initials: I
authors.lastname: Pljesa
authors.forename: Milica
authors.initials: M
authors.lastname: Berisavac
authors.forename: Tatjana
authors.initials: T
authors.lastname: Simic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Pekmezovic
authors.forename: Vesna
authors.initials: V
authors.lastname: Coric
authors.forename: Sonja
authors.initials: S
authors.lastname: Suvakov
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Stamatovic
authors.forename: Marija
authors.initials: M
authors.lastname: Matic
authors.forename: Bojana
authors.initials: B
authors.lastname: Gutic
authors.forename: Sanja
authors.initials: S
authors.lastname: Milenkovic
authors.forename: Marija
authors.initials: M
authors.lastname: Pljesa-Ercegovac
authors.forename: Ana
authors.initials: A
authors.lastname: Savic-Radojevic
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C484555:GSTA1 protein, human; C496556:GSTP1 protein, human