title: GSTO1*C/GSTO2*G haplotype is associated with risk of transitional cell carcinoma of urinary bladder.
abstract: OBJECTIVE
  To clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) in individual susceptibility to urinary bladder cancer.
  
  
  METHODS
  Case-control study consisting of 187 patients with histologically confirmed transitional cell carcinoma (TCC) of urinary bladder and 140 age- and gender-matched cancer-free controls was carried out. Genotyping of GSTO1 and GSTO2 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
  
  
  RESULTS
  We found that carriers of mutant GSTO2*G/G genotype were at increased risk of the development of TCC (OR 2.6, 95% CI 1.2-5.8, p = 0.041), while GSTO1 rs4925 polymorphism was not significantly associated with TCC risk (p = 0.450). According to smoking status, smokers with GSTO2*G/G genotype had significantly higher risk of TCC of urinary bladder (OR 4.3, 95% CI 1.6-11.2, p = 0.003) compared to wild-type carriers with no smoking history. We further analyzed the effects of GSTO1/GSTO2 haplotypes on TCC risk, based on the linkage disequilibrium found for GSTO1 (rs4925) and GSTO2 (rs156697) (D' = 0.309, p = 0.001). The study subjects with GSTO1*C/GSTO2*G (GSTO1 wild-type/GSTO2 mutant) haplotype were at the highest risk of the development of transitional cell carcinoma of urinary bladder (OR 2.8, 95% CI 1.5-5.2, p = 0.002).
  
  
  CONCLUSIONS
  Our results indicate that GSTO1*C/GSTO2*G haplotype is associated with increased risk of TCC. The modifying effect of GSTO2*G/G genotype on individual susceptibility to TCC is more pronounced, when associated with smoking.
authors.affiliation: Faculty of Medicine, Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Djukic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Simic
authors.forename: Tanja
authors.initials: T
authors.lastname: Radic
authors.forename: Marija
authors.initials: M
authors.lastname: Matic
authors.forename: Marija
authors.initials: M
authors.lastname: Pljesa-Ercegovac
authors.forename: Sonja
authors.initials: S
authors.lastname: Suvakov
authors.forename: Vesna
authors.initials: V
authors.lastname: Coric
authors.forename: Tatjana
authors.initials: T
authors.lastname: Pekmezovic
authors.forename: Ivana
authors.initials: I
authors.lastname: Novakovic
authors.forename: Dejan
authors.initials: D
authors.lastname: Dragicevic
authors.forename: Ana
authors.initials: A
authors.lastname: Savic-Radojevic
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; C490476:GSTO1 protein, human; C492569:GSTO2 protein, human; D005982:Glutathione Transferase