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No evidence for glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 in breast cancer risk

  • Epidemiology
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Abstract

Breast cancer is a complex disease and in recent years a number of breast cancer susceptibility genes have been identified, but the role of low penetrance susceptibility genes has not been completely resolved. Glutathione S-transferases (GSTs) are phase II xenobiotic metabolizing enzymes involved in the detoxification of chemical carcinogens and environmental pollutants and play an important role in cell defense mechanisms against oxidative stress. They have been in the spot light for the investigation of a potential association with breast cancer risk but so far, sparse or even no data for a potential contribution of GSTA2, GSTM2, GSTO, and GSTZ to breast cancer risk are available. We genotyped GSTA2_448_C > G (rs2180314), GSTA2_742_A > C (rs6577), GSTM2_-832_T > C (rs638820), GSTO1_-1242_G > A (rs2164624), GSTO1_419_A > C (rs4925), GSTO2_-183_A > G (rs2297235), GSTO2_342_A > G (rs156697), GSTZ1_-4378_A > G (rs1046428), and GSTZ1_94_G > A (rs3177427) by MALDI-TOF MS in the German GENICA breast cancer case–control collection of 1021 cases and 1015 controls and performed breast cancer risk association in general and with respect to the stratifications: menopausal status, family history of breast or ovarian cancer, use of oral contraceptives, use of hormone therapy, body mass index, and smoking as well as histopathological tumor characteristics including hormone receptor status, grade, histology, and node status. We did not observe any breast cancer risk associations and conclude that it is unlikely that glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 participate in breast cancer susceptibility.

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References

  1. Cox A, Dunning AM, Garcia-Closas M, Balasubramanian S, Reed MW, Pooley KA, Scollen S, Baynes C, Ponder BA, Chanock S, Lissowska J, Brinton L, Peplonska B, Southey MC, Hopper JL, McCredie MR, Giles GG, Fletcher O, Johnson N, dos Santos Silva I, Gibson L, Bojesen SE, Nordestgaard BG, Axelsson CK, Torres D, Hamann U, Justenhoven C, Brauch H, Chang-Claude J, Kropp S, Risch A, Wang-Gohrke S, Schurmann P, Bogdanova N, Dork T, Fagerholm R, Aaltonen K, Blomqvist C, Nevanlinna H, Seal S, Renwick A, Stratton MR, Rahman N, Sangrajrang S, Hughes D, Odefrey F, Brennan P, Spurdle AB, Chenevix-Trench G, Beesley J, Mannermaa A, Hartikainen J, Kataja V, Kosma VM, Couch FJ, Olson JE, Goode EL, Broeks A, Schmidt MK, Hogervorst FB, Veer LJ, Kang D, Yoo KY, Noh DY, Ahn SH, Wedren S, Hall P, Low YL, Liu J, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Sigurdson AJ, Stredrick DL, Alexander BH, Struewing JP, Pharoah PD, Easton DF (2007) A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet 39:352–358

    Article  CAS  PubMed  Google Scholar 

  2. Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R, Wareham N, Ahmed S, Healey CS, Bowman R, Meyer KB, Haiman CA, Kolonel LK, Henderson BE, Le ML, Brennan P, Sangrajrang S, Gaborieau V, Odefrey F, Shen CY, Wu PE, Wang HC, Eccles D, Evans DG, Peto J, Fletcher O, Johnson N, Seal S, Stratton MR, Rahman N, Chenevix-Trench G, Bojesen SE, Nordestgaard BG, Axelsson CK, Garcia-Closas M, Brinton L, Chanock S, Lissowska J, Peplonska B, Nevanlinna H, Fagerholm R, Eerola H, Kang D, Yoo KY, Noh DY, Ahn SH, Hunter DJ, Hankinson SE, Cox DG, Hall P, Wedren S, Liu J, Low YL, Bogdanova N, Schurmann P, Dork T, Tollenaar RA, Jacobi CE, Devilee P, Klijn JG, Sigurdson AJ, Doody MM, Alexander BH, Zhang J, Cox A, Brock IW, MacPherson G, Reed MW, Couch FJ, Goode EL, Olson JE, Meijers-Heijboer H, van den Ouweland A, Uitterlinden A, Rivadeneira F, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Hopper JL, McCredie M, Southey M, Giles GG, Schroen C, Justenhoven C, Brauch H, Hamann U, Ko YD, Spurdle AB, Beesley J, Chen X, Mannermaa A, Kosma VM, Kataja V, Hartikainen J, Day NE, Cox DR, Ponder BA (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447:1087–1093

    Article  CAS  PubMed  Google Scholar 

  3. Cheng TC, Chen ST, Huang CS, Fu YP, Yu JC, Cheng CW, Wu PE, Shen CY (2005) Breast cancer risk associated with genotype polymorphism of the catechol estrogen-metabolizing genes: a multigenic study on cancer susceptibility. Int J Cancer 113:345–353

    Article  CAS  PubMed  Google Scholar 

  4. Raftogianis R, Creveling C, Weinshilboum R, Weisz J (2000) Estrogen metabolism by conjugation. J Natl Cancer Inst Monogr 27:113–124

    CAS  PubMed  Google Scholar 

  5. Salinas AE, Wong MG (1999) Glutathione S-transferases—a review. Curr Med Chem 6:279–309

    CAS  PubMed  Google Scholar 

  6. Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88

    Article  CAS  PubMed  Google Scholar 

  7. Egan KM, Cai Q, Shu XO, Jin F, Zhu TL, Dai Q, Gao YT, Zheng W (2004) Genetic polymorphisms in GSTM1, GSTP1, GSTT1, the risk for breast cancer: results from the Shanghai Breast Cancer Study, meta-analysis. Cancer Epidemiol Biomarkers Prev 13:197–204

    Article  CAS  PubMed  Google Scholar 

  8. Roodi N, Dupont WD, Moore JH, Parl FF (2004) Association of homozygous wild-type glutathione S-transferase M1 genotype with increased breast cancer risk. Cancer Res 64:1233–1236

    Article  CAS  PubMed  Google Scholar 

  9. The MARIE-GENICA consortium on genetic susceptibility for menopausal hormone therapy related breast cancer risk genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women (2009) Breast Cancer Res Treat

  10. Singh V, Parmar D, Singh MP (2008) Do single nucleotide polymorphisms in xenobiotic metabolizing genes determine breast cancer susceptibility, treatment outcomes? Cancer Invest 26:769–783

    Article  CAS  PubMed  Google Scholar 

  11. Johansson AS, Mannervik B (2001) Human glutathione transferase A3–3, a highly efficient catalyst of double-bond isomerization in the biosynthetic pathway of steroid hormones. J Biol Chem 276:33061–33065

    Article  CAS  PubMed  Google Scholar 

  12. Wang L, Xu J, Ji C, Gu S, Lv Y, Li S, Xu Y, Xie Y, Mao Y (2005) Cloning expression, characterization of human glutathione S-transferase Omega 2. Int J Mol Med 16:19–27

    CAS  PubMed  Google Scholar 

  13. Baez S, Segura-Aguilar J, Widersten M, Johansson AS, Mannervik B (1997) Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines, may serve as an antioxidant system preventing degenerative cellular processes. Biochem J 324(Pt 1):25–28

    CAS  PubMed  Google Scholar 

  14. Ni H, Yu XJ, Liu HJ, Lei W, Rengaraj D, Li XJ, Yang ZM (2009) Progesterone regulation of glutathione S-transferase Mu2 expression in mouse uterine luminal epithelium during preimplantation period. Fertil Steril 91:2123–2130

    Article  CAS  PubMed  Google Scholar 

  15. Tanguay RM, Jorquera R, Poudrier J, St-Louis M (1996) Tyrosine its catabolites: from disease to cancer. Acta Biochim Pol 43:209–216

    CAS  PubMed  Google Scholar 

  16. Blackshear PJ, Nairn AC, Kuo JF (1988) Protein kinases 1988: a current perspective. FASEB J 2:2957–2969

    CAS  PubMed  Google Scholar 

  17. Justenhoven C, Pierl CB, Haas S, Fischer HP, Baisch C, Hamann U, Harth V, Pesch B, Bruning T, Vollmert C, Illig T, Dippon J, Ko YD, Brauch H (2007) The CYP1B1_1358_GG genotype is associated with estrogen receptor-negative breast cancer. Breast Cancer Res Treat 111:171–177

    Article  PubMed  Google Scholar 

  18. Pesch B, Ko Y, Brauch H, Hamann U, Harth V, Rabstein S, Pierl C, Fischer HP, Baisch C, Justenhoven C, Ranft U, Bruning T (2005) Factors modifying the association between hormone-replacement therapy, breast cancer risk. Eur J Epidemiol 20:699–711

    Article  PubMed  Google Scholar 

  19. Justenhoven C, Hamann U, Pesch B, Harth V, Rabstein S, Baisch C, Ko Y, Bruning T, Vollmert C, Illig T, Brauch H Breast cancer risk is linked with ERCC2 genotypes and a corresponding haplotype in a German population. Proceedings of the 96th Annual Meeting of the American Association of Cancer Research (AACR), page 960 (#4070), 2005 (2005) Woman in Cancer Research (WICR) Brigid G Leventhal Award 2005

  20. Marahatta SB, Punyarit P, Bhudisawasdi V, Paupairoj A, Wongkham S, Petmitr S (2006) Polymorphism of glutathione S-transferase omega gene, risk of cancer. Cancer Lett 236:276–281

    Article  CAS  PubMed  Google Scholar 

  21. Olsen A, Autrup H, Sorensen M, Overvad K, Tjonneland A (2008) Polymorphisms of glutathione S-transferase A1, O1, breast cancer among postmenopausal Danish women. Eur J Cancer Prev 17:225–229

    Article  CAS  PubMed  Google Scholar 

  22. Smith RA, Curran JE, Weinstein SR, Griffiths LR (2001) Investigation of glutathione S-transferase zeta, the development of sporadic breast cancer. Breast Cancer Res 3:409–411

    Article  CAS  PubMed  Google Scholar 

  23. Silva SN, Azevedo AP, Teixeira V, Pina JE, Rueff J, Gaspar JF (2009) The role of GSTA2 polymorphisms, haplotypes in breast cancer susceptibility: a case-control study in the Portuguese population. Oncol Rep 22:593–598

    CAS  PubMed  Google Scholar 

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Acknowledgment

We are indebted to all women participating in the GENICA study. We gratefully acknowledge support by interviewers as well as physicians and pathologists of the study region. This work was supported by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation of Medical Research, Stuttgart, Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Institute of Pathology, Medical Faculty of the University of Bonn, Deutsches Krebsforschungszentrum, Heidelberg, and Forschungsinstitut für Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung, Bochum, Germany.

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Authors and Affiliations

  1. Dr. Margarte Fischer-Bosch Institute of Clinical Pharmacology, 70376, Stuttgart, Germany

    Irena E. Andonova, Christina Justenhoven, Stefan Winter & Hiltrud Brauch

  2. University of Tübingen, Tübingen, Germany

    Irena E. Andonova, Christina Justenhoven, Stefan Winter & Hiltrud Brauch

  3. Department of Medical Chemistry and Biochemistry, Institute of Experimental Pathology and Parasitology, Bulgarian Academy of Science and Medical University, Sofia, Bulgaria

    Irena E. Andonova

  4. Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Ute Hamann

  5. Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany

    Christian Baisch & Yon-Dschun Ko

  6. BGFA-Research Institute of Occupational Medicine of the German Social Accident Insurance, Ruhr University of Bochum, Bochum, Germany

    Sylvia Rabstein, Anne Spickenheuer, Volker Harth, Beate Pesch & Thomas Brüning

  7. Faculty of Medicine, Sofia University St. Kliment Ohridski, Sofia, Bulgaria

    Varban Ganev

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  1. Irena E. Andonova
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  2. Christina Justenhoven
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  3. Stefan Winter
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  4. Ute Hamann
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  9. Beate Pesch
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  12. Varban Ganev
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  13. Hiltrud Brauch
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Correspondence to Hiltrud Brauch.

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Andonova, I.E., Justenhoven, C., Winter, S. et al. No evidence for glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 in breast cancer risk. Breast Cancer Res Treat 121, 497–502 (2010). https://doi.org/10.1007/s10549-009-0589-5

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  • DOI: https://doi.org/10.1007/s10549-009-0589-5

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