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Basic Research

Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran

Prostate Cancer and Prostatic Diseases volume 14, pages 105–113 (2011)Cite this article

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Abstract

We evaluated the relationship between polymorphisms in the glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 genes and prostate cancer (PCa). PCR-restriction fragment length polymorphism assay was used to genotype the GSTM1, GSTT1, and GSTP1 polymorphisms in 168 PCa cases and 336 frequency matched controls. The GSTM1 null, and GSTT1 null genotypes were associated with an increased odds ratio (OR) for PCa (OR=3.28, 95% confidence interval (CI): 2.47–5.64; P=0.005, and OR=3.21, 95% CI: 2.52–5.64; P=0.005, respectively) (Pcorrected=0.0062). The frequency of GSTP1 Val/Val genotype was 14.3% in cases compared with 2.4% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (OR=3.72, 95% CI: 1.67–5.65; P=0.002). The risk associated with the concurrent absence of both of the genes (OR=4.8, 95% CI: 2.34–6.78) was greater than the product of risk in men with either null (OR=1.52, 95% CI: 0.82–2.31) genotype combinations (P=0.001, Pcorrected=0.0045). The combination of GSTP1 Ile/Val or Val/Val polymorphism with the GSTT1 null and GSTM1 null type resulted in an OR of 6.21 (95% CI: 4.83–16.87) (P=0.0001, Pcorrected=0.0062). A higher frequency of the GSTM1 null genotype and GSTT1 null genotype was observed in patients with Gleason score >7, with an OR for GSTM1 null 4.67 (95% CI: 3.64–7.62; P=0.001) and with an OR for GSTT1 null 3.62 (95% CI: 2.31–5.74; P=0.004). The results obtained demonstrated that simultaneous presence of three potentially risk alleles (GSTM1 null, GSTT1 null and GSTP1 Val) lead to a significant OR increase for PCa.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T et al. Cancer statistics, 2008. CA Cancer J Clin 2008; 58: 71–96.

    Article  PubMed  Google Scholar 

  2. Postma R, Schroder FH . Screening for prostate cancer. Eur J Cancer 2005; 41: 825–833.

    Article  CAS  PubMed  Google Scholar 

  3. Bosland M . Sex steroids and prostate carcinogenesis integrated, multifactorial working hypothesis. Ann NY Acad Sci 2006; 1089: 168–176.

    Article  CAS  PubMed  Google Scholar 

  4. Safarinejad MR . Population-based screening for prostate cancer by measuring free and total serum prostate-specific antigen in Iran. Ann Oncol 2006; 17: 1166–1171.

    Article  CAS  PubMed  Google Scholar 

  5. Hosseini SY, Moharramzadeh M, Ghadian AR, Hooshyar H, Lashay AR, Safarinejad MR . Population-based screening for prostate cancer by measuring total serum prostate-specific antigen in Iran. Int J Urol 2007; 14: 406–411.

    Article  PubMed  Google Scholar 

  6. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M et al. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000; 343: 78–85.

    Article  CAS  PubMed  Google Scholar 

  7. Hughes C, Murphy A, Martin C, Sheils O, O'Leary J . Molecular pathology of prostate cancer. J Clin Pathol 2005; 58: 673–684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kvitko K, Nunes JC, Weimer TA, Salzano FM, Hutz MH . Cytochrome P4501A1 polymorphisms in South American Indians. Hum Biol 2000; 72: 1039–1043.

    CAS  PubMed  Google Scholar 

  9. Karagas MR, Park S, Warren A, Hamilton J, Nelson HH, Mott LA et al. Gender, smoking, glutathione S-transferase variants, and bladder cancer incidence: a population based study. Cancer Lett 2005; 219: 63–69.

    Article  CAS  PubMed  Google Scholar 

  10. Mao JX, Buolamwini J . Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem 1997; 272: 10004–10012.

    Article  PubMed  Google Scholar 

  11. Lee WH, Morton RA, Epstein JI, Brooks JD, Campbell PA, Bova GS et al. Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proc Natl Acad Sci USA 1994; 91: 11733–11737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sivonová M, Waczulíková I, Dobrota D, Matáková T, Hatok J, Racay P et al. Polymorphisms of glutathione-S-transferase M1, T1, P1 and the risk of prostate cancer: a case-control study. J Exp Clin Cancer Res 2009; 28: 32.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Agalliu I, Lin DW, Salinas CA, Feng Z, Stanford JL . Polymorphisms in the glutathione S-transferase M1, T1, and P1 genes and prostate cancer prognosis. Prostate 2006; 66: 1535–1541.

    Article  CAS  PubMed  Google Scholar 

  14. Agalliu I, Langeberg WJ, Lampe JW, Salinas CA, Stanford JL . Glutathione S-transferase M1, T1, and P1 polymorphisms and prostate cancer risk in middle-aged men. Prostate 2006; 66: 146–156.

    Article  CAS  PubMed  Google Scholar 

  15. Srivastava DS, Mandhani A, Mittal B, Mittal RD . Genetic polymorphism of glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and susceptibility to prostate cancer in Northern India. BJU Int 2005; 95: 170–173.

    Article  CAS  PubMed  Google Scholar 

  16. Komiya Y, Tsukino H, Nakao H, Kuroda Y, Imai H, Katoh T . Human glutathione S-transferase A1, T1, M1, and P1 polymorphisms and susceptibility to prostate cancer in the Japanese population. J Cancer Res Clin Oncol 2005; 131: 238–242.

    Article  CAS  PubMed  Google Scholar 

  17. Nakazato H, Suzuki K, Matsui H, Koike H, Okugi H, Ohtake N et al. Association of genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) with familial prostate cancer risk in a Japanese population. Anticancer Res 2003; 23: 2897–2902.

    CAS  PubMed  Google Scholar 

  18. Kidd LC, Woodson K, Taylor PR, Albanes D, Virtamo J, Tangrea JA . Polymorphisms in glutathione-S-transferase genes (GST-M1, GST-T1 and GST-P1) and susceptibility to prostate cancer among male smokers of the ATBC cancer prevention study. Eur J Cancer Prev 2003; 12: 317–320.

    Article  PubMed  Google Scholar 

  19. Kote-Jarai Z, Easton D, Edwards SM, Jefferies S, Durocher F, Jackson RA et al. Relationship between glutathione S-transferase M1, P1 and T1 polymorphisms and early onset prostate cancer. Pharmacogenetics 2001; 11: 325–330.

    Article  CAS  PubMed  Google Scholar 

  20. Gsur A, Haidinger G, Hinteregger S, Bernhofer G, Schatzl G, Madersbacher S et al. Polymorphisms of glutathione-S-transferase genes (GSTP1, GSTM1 and GSTT1) and prostate-cancer risk. Int J Cancer 2001; 95: 152–155.

    Article  CAS  PubMed  Google Scholar 

  21. Lavender NA, Benford ML, VanCleave TT, Brock GN, Kittles RA, Moore JH et al. Examination of polymorphic glutathione S-transferase (GST) genes, tobacco smoking and prostate cancer risk among men of African descent: a case-control study. BMC Cancer 2009; 9: 397.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Safarinejad MR, Shafiei N, Safarinejad S . The association of glutathione-S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) with idiopathic male infertility. J Hum Genet 2010; 55: 565–570.

    Article  CAS  PubMed  Google Scholar 

  23. Liu YJ, Huang PL, Chang YF, Chen YH, Chiou YH, Xu ZL et al. GSTP1 genetic polymorphism is associated with a higher risk of DNA damage in pesticide-exposed fruit growers. Cancer Epidemiol Biomarkers Prev 2006; 15: 659–666.

    Article  CAS  PubMed  Google Scholar 

  24. Taylor JA, Hirvonen A, Watson M, Pittman G, Mohler JL, Bell DA . Association of prostate cancer with vitamin D receptor gene polymorphism. Cancer Res 1996; 56: 4108–4110.

    CAS  PubMed  Google Scholar 

  25. Wadelius M, Autrup JL, Stubbins MJ, Andersson SO, Johansson JE, Wadelius C et al. Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer. Pharmacogenetics 1999; 9: 333–340.

    Article  CAS  PubMed  Google Scholar 

  26. Rebbeck TR . Molecular epidemiology of the human glutathione S-transferase genotypes and GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 1997; 6: 733–743.

    CAS  PubMed  Google Scholar 

  27. Harries LW, Stubbins MJ, Forman D, Howard GC, Wolf CR . Identification of genetic polymorphisms at the glutathione S-transferase p locus and association with susceptibility to bladder, testicular, and prostate cancer. Carcinogenesis 1997; 18: 641–644.

    Article  CAS  PubMed  Google Scholar 

  28. Lafunte A, Pujol F, Carretero P, Villa JP, Cuchi A . Human glutathione S-transferase m (GSTm) deficiency as a marker for the susceptibility to bladder and larynx cancer among smokers. Cancer Lett 1993; 68: 49–54.

    Article  Google Scholar 

  29. Lai MT, Chen RH, Tsai FJ, Wan L, Chen WC . Glutathione S-transferase M1 gene but not insulin-like growth factor-2 gene or epidermal growth factor gene is associated with prostate cancer. Urol Oncol 2005; 23: 225–229.

    Article  CAS  PubMed  Google Scholar 

  30. Lin HJ, Han CY, Bernstein DA, Hsiao W, Lin BK, Hardy S . Ethnic distribution of the glutathione transferase Mu 1–1 (GSTM1) null genotype in 1473 individuals and application to bladder cancer susceptibility. Carcinogenesis 1994; 15: 1077–1081.

    Article  CAS  PubMed  Google Scholar 

  31. Murata M, Shiraishi T, Fukutome K, Watanabe M, Nagao M, Kubota Y et al. Cytochrome P4501A1 and glutathione S transferase M1 genotypes as risk factors for prostate cancer in Japan. Jpn J Clin Oncol 1998; 28: 657–660.

    Article  CAS  PubMed  Google Scholar 

  32. Kidd LC, Woodson K, Taylor PR, Albanes D, Virtamo J, Tangrea JA . Polymorphisms in glutathione S-transferase (GST-M1, GST-T1 and GST-p1) and susceptibility to prostate cancer among male smokers of the ATBC cancer prevention study. Eur J Cancer Prev 2003; 12: 317–320.

    Article  PubMed  Google Scholar 

  33. Steinhoff C, Franke KH, Golka K, Thier R, Römer HC, Rötzel C et al. Glutathione transferase isozyme genotypes in patients with prostate and bladder carcinoma. Arch Toxicol 2000; 74: 521–526.

    Article  CAS  PubMed  Google Scholar 

  34. Rebbeck TR, Walker AH, Jaffe JM, White DL, Wein AJ, Malkowicz SB . Glutathione S-transferase-mu (GSTM1) and—theta (GSTT1) genotypes in the etiology of prostate cancer. Cancer Epidemiol Biomarkers Prev 1999; 8: 283–287.

    CAS  PubMed  Google Scholar 

  35. Garte S, Gaspari L, Alexandrie AK, Ambrosone C, Autrup H, Autrup JL et al. Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev 2001; 10: 1239–1248.

    CAS  PubMed  Google Scholar 

  36. Autrup JL, Thomassen LH, Olsen JH, Wolf H, Autrup H . Glutathione S-transferases as risk factors in prostate cancer. Eur J Cancer Prev 1999; 8: 525–532.

    Article  CAS  PubMed  Google Scholar 

  37. Shepard TF, Platz EA, Kantoff PW, Nelson WG, Isaacs WB, Freije D et al. No association between the I105V polymorphism of the glutathione S-transferase P1 gene (GSTP1) and prostate cancer risk: a prospective study. Cancer Epidemiology Biomarkers Prev 2000; 9: 1267–1268.

    CAS  Google Scholar 

  38. Luscombe CJ, French ME, Liu S, Saxby MF, Farrell WE, Jones PW et al. Glutathione S-transferase GSTP1 genotypes are associated with response to androgen ablation therapy in advanced prostate cancer. Cancer Detect Prev 2002; 26: 376–380.

    Article  CAS  PubMed  Google Scholar 

  39. Mao GE, Morris G, Lu QY, Cao W, Reuter VE, Cordon-Cardo C et al. Glutathione S-transferase P1 Ile105Val polymorphism, cigarette smoking and prostate cancer. Cancer Detect Prev 2004; 28: 368–374.

    Article  CAS  PubMed  Google Scholar 

  40. Shirai T, Sano M, Tamano S, Takahashi S, Hirose M, Futakuchi M et al. The prostate: a target for carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) derived from cooked foods. Cancer Res 1997; 57: 195–198.

    CAS  PubMed  Google Scholar 

  41. Dijkman GA, Debruyne FM . Epidemiology of prostate cancer. Eur Urol 1996; 30: 281–295.

    Article  CAS  PubMed  Google Scholar 

  42. Strachen T, Read AP (eds) Genetic mapping of complex characters. 2nd edn. John Wiley & Sons: New York (NY), 1999; p 287, chapter 12.

  43. Ketterer B . Protective role of glutathione and glutathione transferases in mutagenesis and carcinogenesis. Mutat Res 1988; 202: 343–361.

    Article  CAS  PubMed  Google Scholar 

  44. Stoehlmacher J, Park DJ, Zhang W, Groshen S, Tsao-Wei DD, Yu MC et al. Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. J Natl Cancer Inst 2002; 94: 936–942.

    Article  CAS  PubMed  Google Scholar 

  45. Board PG . Biochemical genetics of glutathione-S-transferase in man. Am J Hum Genet 1981; 33: 36–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Hickey K, Do KA, Green A . Smoking and prostate cancer. Epidemiol Rev 2001; 23: 115–125.

    Article  CAS  PubMed  Google Scholar 

  47. Fowler Jr JE, Sanders J, Bigler SA, Rigdon J, Kilambi NK, Land SA . Percent free prostate specific antigen and cancer detection in black and white men with total prostate specific antigen 2.5–9.9 ng/ml. J Urol 2000; 163: 1467–1470.

    Article  PubMed  Google Scholar 

  48. Fowler Jr JE, Bigler SA, Farabaugh PB . Prospective study of cancer detection in black and white men with normal digital rectal examination but prostate specific antigen equal or greater than 4.0 ng/ml. Cancer 2002; 94: 1661–1667.

    Article  PubMed  Google Scholar 

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  1. Private Practice of Urology and Andrology, Tehran, Iran

    M R Safarinejad, N Shafiei & S H Safarinejad

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Safarinejad, M., Shafiei, N. & Safarinejad, S. Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran. Prostate Cancer Prostatic Dis 14, 105–113 (2011). https://doi.org/10.1038/pcan.2010.54

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