Previous studies suggest that bladder cancer risk may vary with GST genotype but these results are inconsistent. The aim of this study was to explore whether GSTM1, GSTT1 and GSTP polymorphisms were associated with increased bladder cancer risk in an Egyptian population. GSTM1, GSTT1 and GSTP1 genotype frequencies were determined in bladder cancer cases (n=72) and healthy controls with no history of malignancies (n=82) using PCR-based techniques. The GSTT1*2 genotype was particularly associated with increased risk (OR 2.71, 95%CI 1.27–5.73) and the GSTM1*2 genotype to a lesser extent (OR 1.63, 95%CI 0.85–3.10). 18.1% of cases but only 7.3% of controls were GSTP1*B*B homozygotes (OR 2.38, 95%CI 0.83–6.87). The presence of two or more a priori at-risk genotypes was associated with increased bladder cancer risk (OR 2.42; 95%CI 1.47–3.97). These results suggest that polymorphisms in the GST genes are associated with increased risk of bladder cancer among Egyptians.
KahanE., IbrahimA.S., El NajjarK.. Cancer patterns in the Middle East—special report from the Middle East Cancer Society.Acta Oncol1997; 36: 631–6.
2.
BedwaniR., el-KhwskyF., La VecchiaC., BoffettaP., LeviF.. Descriptive epidemiology of bladder cancer in Egypt.Int J Cancer1993; 55: 351–2.
3.
MadyE.A.. Cytokeratins as serum markers in Egyptian bladder cancer. A comparison of CYFRA 21–1, TPA and TPS.Int J Biol Markers2001; 16: 130–5.
4.
MostafaM.H., SheweitaS.A., O'ConnorP.J.. Relationship between schistosomiasis and bladder cancer.Clin Microbiol Rev1999; 12: 97–111.
5.
BedwaniR., el-KhwskyF., RenganathanE.. Epidemiology of bladder cancer in Alexandria, Egypt: tobacco smoking.Int J Cancer1997; 73: 64–7.
6.
ColesB.F., KadlubarF.F.. Detoxification of electrophilic compounds by glutathione S-transferase catalysis: determinants of individual response to chemical carcinogens and chemotherapeutic drugs?.Biofactors2003; 17: 115–30.
7.
HayesJ.D., PulfordD.J.. The glutathione S-transferase supergene family: regulation of GST and the contribution of the enzyme to cancer chemoprotection and drug resistance.Crit Rev Biochem Mol Biol1995; 30: 445–600.
8.
RebbeckT.R.. Molecular epidemiology of the human glutathione s-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility.Cancer Epidemiol Biomarkers Prevent1997; 6: 733–43.
9.
WhalenR., BoyerT.D.. Human glutathione S-transferases.Semin Liver Dis1998; 18: 345–58.
10.
HuX., JiX., SrivastavaS.K.. Mechanism of differential catalytic efficiency of two polymorphic forms of human glutathione S-transferase P1–1 in the glutathione conjugation of carcinogenic diol epoxide of chrysene.Arch Biochem Biophys1997; 345: 32–8.
11.
EngelL.S., TaioliE., PfeifferR.. Pooled analysis and meta-analysis of glutathione S-transferase M1 and bladder cancer: a HuGE review.Am J Epidemiol2002; 156: 95–109.
12.
HungR.J., BoffettaP., BrennanP.. GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population.Int J Cancer2004; 110: 598–604.
13.
KimW.J., KimH., KimC.H.. GSTT1-null genotype is a protective factor against bladder cancer.Urology2002; 60: 913–8.
14.
TorunerG.A., AkyerliC., UcarA.. Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and bladder cancer susceptibility in the Turkish population.Arch Toxicol2001; 75: 459–64.
15.
LafuenteA., ZakaharyM.M., el AzizM.A.. Influence of smoking in the glutathione-S-transferase M1 deficiency-associated risk for squamous cell carcinoma of the bladder in schistosomiasis patients in Egypt.Br J Cancer1996; 74: 836–8.
16.
AnwarW.A., Abdel RahmanS.Z., El ZeinR.A., MostafaH.M., AuW.W.. Genetic polymorphism of GSTM1, CYP2E1 and CYP2D6 in Egyptian bladder cancer patients.Carcinogenesis1996; 17: 1923–9.
17.
Abdel RahmanS.Z., AnwarW.A., Abdel AalW.E., MostafaH.M., AuW.W.. GSTM1 and GSTT1 genes are potential risk modifiers for bladder cancer.Cancer Detect Prev1998; 22: 129–38.
18.
LewisS.J., CherryN.M., McLNivenR., BarberP.V., PoveyA.C.. GSTM1, GSTT1 and GSTP1 polymorphisms and lung cancer risk.Cancer Lett2002; 180: 165–71.
19.
de VriesH.G., ColleeJ.M., van VeldhuizenM.H.. Validation of the determination of deltaF508 mutations of the cystic fibrosis gene in over 11,000 mouthwashes.Hum Genet1996; 97: 334–6.
20.
Abdel RahmanS.Z., el ZeinR.A., AnwarW.A., AuW.W.. A multiplex PCR procedure for polymorphic analysis of GSTM1 and GSTT1 genes in population studies.Cancer Lett1996; 107: 229–33.
21.
SmithM.T., EvansC.G., Doane SetzerP., CastroV.M., TahirM.K., MannervikB.. Denitrosation of 1,3-bis(2-chloroethyl)-1-nitrosourea by class mu glutathione transferases and its role in cellular resistance in rat brain tumor cells.Cancer Res1989; 49: 2621–5.
