No abstract

ObjectiveTo examine the association of six glutathione transferase (GST) gene polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1, GSTA1/rs3957357) with the survival of patients with muscle invasive bladder cancer and the genotype modifying effect on chemotherapy.Patients and MethodsA total of 105 patients with muscle invasive bladder cancer were included in the study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier analysis was performed to assess differences in survival.Results GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P = 0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively) and significantly influenced the overall survival. There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a significant effect on the survival in the subgroup of patients who received chemotherapy (P = 0.006).Conclusion GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer.

izolovana iz krvi 182 kontrolna subjekta i 76 bolesnika sa KBP. Polimorfizam GSTM1 i GSTT1 je odre|ivan metodom PCR-a. Dobijeni rezultati su analizirani u odnosu na faktore rizika za KBP, uklju~uju}i pu{enje i profesionalnu izlo`e nost. U~estalost GSTM1-nultog genotipa je bila vi{a kod bolesnika sa KBP (60,5%) nego kod kontrola (47,2%). Prisustvo GSTT1-nultog genotipa je utvr|eno kod 28,6% kontrola i 27,6% bolesnika sa KBP. Nosioci GSTM1-nultog genotipa imaju 1.9-puta ve}i rizik za KBP (95% CI: 1,06-3,33). Prisustvo GSTT1 aktivnog genotipa je udru `eno sa pove}anim rizikom za KBP kod profesionalno izlo `enih subjekata ka da su kao referentna grupa uzeti neizlo`eni nosici GSTT1-nultog genotipa (OR: 2,48; 95% CI: 1,05-5,86). Nije otkrivena povezanost izme |u nedo statka aktivne forme GSTM1 i GSTT1 i pu{e -nja kod obolelih od KBP. Studija izvedena u Srbiji je pokazala da prisustvo GSTM1 aktivnog genotipa {titi od nastanka KBP, dok prisustvo GSTT1 aktivnog geno tipa pove}ava rizik kod profesionalno izlo`enih osoba.Klju~ne re~i: faktori rizika, glutation S-transferaze, karcinom bubre`nog parenhima, polimorfizamList of non-standard abbreviations: GST -glutathione S-transferase; RCC -renal cell carcinoma; OR -odds ratio, CIconfidence interval Summary: Members of the glutathione S-transferase (GST) superfamily exhibit polymorphic expression. GSTs are investigated as biomarkers of risk for various cancers, including renal cell carcinoma (RCC). The aim of this study was to test the association between GSTM1 and GSTT1 polymorphism and susceptibility to RCC, independently or in conjunction with known risk factors. Genomic DNA was isolated from 182 controls and 76 patients with RCC. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. Data obtained were analyzed with respect to RCC risk factors including smoking and occupational exposure. The frequency of GSTM1-null genotype was higher in patients with RCC (60.5%) compared to controls (47.2%). GSTT1-null genotype was found in 28.6% controls and 27.6% of cases. GSTM1-null individuals exhibit 1.9-fold increased risk of RCC (95% CI: 1.06-3.33). The presence of GSTT1 active genotype was associated with increased risk of RCC in occupationally exposed sub jects when unexposed GSTT1-null subjects were used as a comparison group (OR: 2.48; 95% CI: 1.05-5.86). No association was found between the inactive form of GSTM1 and GSTT1 and smoking in RCC patients. In a Serbian cohort of patients, the presence of a GSTM1 active geno type is protective against RCC, whereas a GSTT1 active geno type increases RCC risk in occupationally exposed subjects.

Detailed preoperative evaluation is essential in prevention of perioperative complications. As thorough anamnesis, physical examination and standard laboratory investigation do not contribute much in prediction of perioperative complications and outcome, and detection of tumor markers is also insufficient in means of prognosis, some molecular marker have emerged lately as prognostic markers in surgery. Recent data on pathophysiological processes stress response, derangements of hemostasis, in sepsis or in thromboembolism as well as in malignancy, indicate that presence or elevation of some molecular markers of fibrinolysis can indicate possibility of perioperative complications and even predict outcome. As it is evident that neoplastic cells enhance thrombin and other procoagulant production, detection of degree of activation of coagulation and fibrinolysis can contribute in prediction of treatment outcome in patients with bladder carcinoma scheduled for radical surgical procedures.

In patients with CRF the cumulative effect of the drug was registered, with a prolonged recovery time from NMB in relation to the patients with normal renal function.