Glutathione S-transferase (GST) genotype distribution.

<p>Glutathione S-transferase (GST) genotype distribution.</p

<i>GST</i> genotypes in relation to the risk of cRCC.

<p><i>GST</i> genotypes in relation to the risk of cRCC.</p

Survival analysis Kaplan–Meier curves according to <i>GSTO2</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).

<p>Survival analysis Kaplan–Meier curves according to <i>GSTO2</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).</p

Patient characteristics at study entry.

<p>Patient characteristics at study entry.</p

<i>GSTT1, GSTP1, GSTO1, GSTO2, GSTM1</i> and <i>GSTA1</i> polymorphisms as the predictors for overall mortality among 101 patients with muscle invasive TCC after 5 yrs of follow-up by the Cox proportional hazards regression.

<p>Abbreviations: CI, Confidence Interval; HR, Hazard Ratio.</p>a<p>Adjusted for age and gender.</p>b<p>Adjusted for the covariates in Model 1 plus an additional adjustment for grade.</p

Combined effect of <i>GST</i> genotypes on risk of cRCC.

<p>Combined effect of <i>GST</i> genotypes on risk of cRCC.</p

Baseline characteristic of patients with cRCC and respective controls.

<p>Baseline characteristic of patients with cRCC and respective controls.</p

PCR: primer sequences, PCR conditions, restriction enzymes and fragment lengths.

<p>PCR: primer sequences, PCR conditions, restriction enzymes and fragment lengths.</p

Survival analysis Kaplan–Meier curves according to <i>GSTO1</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).

<p>Survival analysis Kaplan–Meier curves according to <i>GSTO1</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).</p

Combined <i>GSTM1-Null</i>, <i>GSTT1-Active</i>, <i>GSTA1 Low-Activity</i> and <i>GSTP1-Variant</i> Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma

<div><p>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. <i>GSTA1</i>, <i>GSTM1</i>, <i>GSTP1</i> and <i>GSTT1</i> 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 <i>GST</i> genotype and risk of cRCC development was found for the <i>GSTM1-null</i> and <i>GSTP1-variant</i> genotype (p = 0.02 and p<0.001, respectively). Furthermore, 22% of all recruited cRCC patients were carriers of combined <i>GSTM1-null</i>, <i>GSTT1-active</i>, <i>GSTA1-low activity</i> and <i>GSTP1-variant</i> genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04). Significant association between <i>GST</i> genotype and cRCC risk in smokers was found only for the <i>GSTP1</i> genotype, while <i>GSTM1-null/GSTP1-variant/GSTA1 low-activity</i> 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 <i>GSTM1-null</i> genotype had significantly higher concentration of BPDE-DNA adducts in comparison with <i>GSTM1-active</i> cRCC smokers (p = 0.05). <i>GSTM1</i>, <i>GSTT1</i>, <i>GSTA1</i> and <i>GSTP1</i> polymorphisms might be associated with the risk of cRCC, with special emphasis on <i>GSTM1-null</i> and <i>GSTP1-variant</i> genotypes. Combined <i>GSTM1-null</i>, <i>GSTT1-active</i>, <i>GSTA1 low activity</i> and <i>GSTP1-variant</i> genotypes might be considered as “risk-carrying genotype combination” in cRCC.</p></div