title: Common Polymorphisms in GSTA1, GSTM1 and GSTT1 Are Associated with Susceptibility to Urinary Bladder Cancer in Individuals from Balkan Endemic Nephropathy Areas of Serbia.
abstract: Balkan endemic nephropathy (BEN) is a chronic familial form of interstitial nephritis that might eventually lead to end stage renal disease. This nephropathy affects individuals living along of the Danube River and its tributaries in Serbia, Bosnia, Croatia, Bulgaria and Romania. The increased incidence of urinary tract tumors in the BEN areas is well described, but its specific genetic predisposition is still unclear. Certain nephrocarcinogenic compounds, including those associated with BEN, are metabolized by glutathione S-transferase (GST) superfamily of phase II detoxication enzymes. Importantly, the GST-mediated detoxification may result in formation of more toxic compounds. We examined the association of common GST polymorphisms and bladder cancer (BC) risk in individuals from BEN areas in Serbia. A hospital-based case-control study included 201 BC cases (67 from BEN region) and 122 controls. Each polymorphism was identified by a PCR-based method. Individuals from BEN region with low-expression GSTA1 genotype (AB+BB) exhibited a 2.6-fold higher BC risk compared to those with GSTA1 (AA) genotype who were from non-BEN region (OR = 2.60, p = 0.015). In contrast, carriers of GSTM1-active genotype from BEN region had a 2.9-fold increased BC risk compared to those with GSTM1-active genotype from non-BEN region (OR = 2.90, p = 0.010). Likewise, carriers with GSTT1-active genotype from BEN region exhibited 2.1-fold higher BC risk compared to those from non-BEN region with GSTT1-active genotype (OR = 2.10, p = 0.027). Thus, common polymorphisms in GSTA1, GSTM1 and GSTT1 are associated with susceptibility to BC in individuals from BEN areas of Serbia.
authors: Institute of Medical and Clinical Biochemistry.
authors: Marija
authors: M
authors: Matic
authors: Biljana
authors: B
authors: Dragicevic
authors: Tatjana
authors: T
authors: Pekmezovic
authors: Sonja
authors: S
authors: Suvakov
authors: Ana
authors: A
authors: Savic-Radojevic
authors: Marija
authors: M
authors: Pljesa-Ercegovac
authors: Dejan
authors: D
authors: Dragicevic
authors: Jelena
authors: J
authors: Smiljic
authors: Tatjana
authors: T
authors: Simic
mesh_terms: D001449:Balkan Nephropathy / Q000235:genetics*; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D055771:Serbia; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics*
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C484555:GSTA1 protein, human