title: GSTM1-null and GSTA1-low activity genotypes are associated with enhanced oxidative damage in bladder cancer.
abstract: OBJECTIVE
  To examine the association between gene variants of the detoxifying and antioxidant enzymes glutathione transferase M1 (GSTM1) and glutathione transferase A1 (GSTA1) and the extent of oxidative damage in patients with transitional cell carcinoma (TCC) of the urinary bladder.
  
  
  METHODS
  GSTM1 deletion polymorphism was identified by polymerase chain reaction, and the restriction fragment length polymorphism method was used for the single nucleotide polymorphism of GSTA1. Enzyme immunoassay was used to determine markers of DNA (8-hydroxy-2′-deoxyguanosine, 8-OHdG) and lipid (8-epiprostaglandin F2α) oxidative damage in the urine of 80 TCC patients and 60 age-matched controls.
  
  
  RESULTS
  Urinary 8-OHdG and 8-epi-prostaglandin F2α concentrations in TCC patients were significantly higher than in controls (P=0.043 and 0.001, respectively). GSTM1 and GSTA1 polymorphisms influence vulnerability to both DNA and lipid oxidation, with the GSTM1-null gene variant having a more pronounced effect. A significant effect of combined GSTM1 and GSTA1 genotypes on the extent of oxidative damage was found only for 8-OHdG (P=0.018). In addition, TCC patients with the most malignant tumors exhibited significantly higher frequencies of GSTM1-null or GSTA1-low activity genotypes, associated with a twofold increase in urinary 8-OHdG concentration (P=0.044).
  
  
  CONCLUSIONS
  Our results suggest that absent GSTM1 or reduced GSTA1 antioxidant activity may increase the accumulation of oxidative DNA damage, thereby contributing to the malignant potential of TCC.
authors: Faculty of Medicine, Institute of Medical and Clinical Biochemistry, University of Belgrade, Serbia.
authors: Ana
authors: A
authors: Savic-Radojevic
authors: Tatjana
authors: T
authors: Djukic
authors: Tatjana
authors: T
authors: Simic
authors: Marija
authors: M
authors: Pljesa-Ercegovac
authors: Dejan
authors: D
authors: Dragicevic
authors: Tatjana
authors: T
authors: Pekmezovic
authors: Milica
authors: M
authors: Cekerevac
authors: Veljko
authors: V
authors: Santric
authors: Marija
authors: M
authors: Matic
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007124:Immunoenzyme Techniques; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D014408:Biomarkers, Tumor; D003849:Deoxyguanosine; D015237:Dinoprost; D005982:Glutathione Transferase; C075750:8-epi-prostaglandin F2alpha; C484555:GSTA1 protein, human
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