title: Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.
abstract: OBJECTIVE
  We investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients.
  
  
  METHODS
  A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR) with corresponding 95% confidence interval (95%CI) was calculated.
  
  
  RESULTS
  The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032). The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001). The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001). The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p = 0.002). Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067).
  
  
  CONCLUSIONS
  Null or low-activity genotypes of the glutathione S-transferase A1, T1, and P1 did not contribute independently towards the risk of bladder cancer in males. However, in association with occupational exposure, low activity glutathione S-transferase A1 and glutathione S-transferase M1-null as well as glutathione S-transferase T1-active genotypes increase individual susceptibility to bladder cancer.
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Marija G
authors.initials: MG
authors.lastname: Matic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vesna M
authors.initials: VM
authors.lastname: Coric
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Savic-Radojevic
authors.affiliation: Institute of Occupational Health, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Petar V
authors.initials: PV
authors.lastname: Bulat
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Marija S
authors.initials: MS
authors.lastname: Pljesa-Ercegovac
authors.affiliation: Clinic of Urology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Dejan P
authors.initials: DP
authors.lastname: Dragicevic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Tatjana I
authors.initials: TI
authors.lastname: Djukic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Tatjana P
authors.initials: TP
authors.lastname: Simic
authors.affiliation: Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Tatjana D
authors.initials: TD
authors.lastname: Pekmezovic
mesh_terms: D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D010575:Pesticides / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D055771:Serbia; D012997:Solvents / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics*
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D010575:Pesticides; D012997:Solvents; C413545:glutathione S-transferase T1; C484555:GSTA1 protein, human; C496556:GSTP1 protein, human