title: Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma.
abstract: The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and p<0.001, respectively). Furthermore, 22% of all recruited cRCC patients were carriers of combined GSTM1-null, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04). Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as "risk-carrying genotype combination" in cRCC.
authors: Institute of Medical and Clinical Biochemistry, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Vesna M
authors: VM
authors: Coric
authors: Institute of Medical and Clinical Biochemistry, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Tatjana P
authors: TP
authors: Simic
authors: Institute of Epidemiology, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Tatjana D
authors: TD
authors: Pekmezovic
authors: Institute of Pathology, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Gordana M
authors: GM
authors: Basta-Jovanovic
authors: Institute of Medical and Clinical Biochemistry, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Ana R
authors: AR
authors: Savic Radojevic
authors: Institute of Pathology, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Sanja M
authors: SM
authors: Radojevic-Skodric
authors: Institute of Medical and Clinical Biochemistry, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Marija G
authors: MG
authors: Matic
authors: Clinic of Urology, Clinical Center of Serbia, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Dejan P
authors: DP
authors: Dragicevic
authors: Faculty of Medicine, University in Belgrade, Serbia.
authors: Tanja M
authors: TM
authors: Radic
authors: Institute of Pathology, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Ljiljana M
authors: LM
authors: Bogdanovic
authors: Clinic of Urology, Clinical Center of Serbia, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Zoran M
authors: ZM
authors: Dzamic
authors: Institute of Medical and Clinical Biochemistry, Belgrade, Serbia.|Faculty of Medicine, University in Belgrade, Serbia.
authors: Marija S
authors: MS
authors: Pljesa-Ercegovac
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000235:genetics
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C484555:GSTA1 protein, human; C496556:GSTP1 protein, human