Skip to main content

Advertisement

Log in

Glutathione S-transferase M1 and T1 polymorphism and response to neoadjuvant chemotherapy (CAF) in breast cancer patients

  • Original Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Purpose

Response to neoadjuvant chemotherapy (NACT) for breast cancer patients cannot be predicted; however, polymorphism of the glutathione S-transferase genes GSTM1 and GSTT1 can modify the response to chemotherapy. The aim of this study was to establish whether there is an association between the polymorphism of GSTM1 and GSTT1 and response to NACT.

Methods

The subjects of this study were 45 patients with locally advanced breast cancer (LABC), who received the cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) regimen as NACT. We analyzed the relationship between the genotypes and responses to chemotherapy.

Results

The response rates to chemotherapy were better, although not significantly so, in patients with the GSTM1 and GSTT1 null genotypes (odds ratio [OR] 2.06 and 1.45). Similar findings were noted in patients with either or both of the null genotypes (OR 2.67 and 1.16). Among the responders, patients with the GSTM1 and GSTT1 null genotypes had higher rates of complete response following chemotherapy than those with one or more active allele (OR 1.8 and 1.3), although the difference was not significant.

Conclusions

There was an association between the polymorphism of glutathione S-transferases and responses to chemotherapy, but the differences were not significant. However, larger studies are needed to investigate the role and efficiency of GST polymorphism in predicting response to chemotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hortobagyi GN, de la Garza Salazar J, Pritchard K, Amadori D, Haidinger R, Hudis CA, et al. The global breast cancer burden: variations in epidemiology and survival. Clin Breast Cancer 2005;6:391–401.

    Article  PubMed  Google Scholar 

  2. Bafaloukos D. Neo-adjuvant therapy in breast cancer. Ann Oncol 2005;16(s-2):174–181.

    Google Scholar 

  3. Pusztai L, Symmans FW, Hortobagyi GN. Development of pharmacogenomic markers to select preoperative chemotherapy for breast cancer. Breast Cancer 2005;12:73–85.

    Article  PubMed  Google Scholar 

  4. Vyzula R, Dusek L, Zaloudík J, Demlová R, Klimes D, Selvekerová S. Breast cancer and neoadjuvant therapy: any predictive marker? Neoplasma 2004;51:471–480.

    PubMed  CAS  Google Scholar 

  5. Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer 2003;88:406–412.

    Article  PubMed  CAS  Google Scholar 

  6. Bosh TM, Meijerman I, Beijnen JH, Schellens JH. Genetic polymorphisms of drug-metabolizing enzymes and drug transporters in the chemotherapeutic treatment of cancer. Clin Pharmacokinet 2006;45:253–285.

    Article  Google Scholar 

  7. Stearns V, Davisson NE, Flockhart DA. Pharmacogenetics in the treatment of breast cancer. Pharmacogenenomics J 2004;4:143–153.

    Article  CAS  Google Scholar 

  8. Petros WP, Hopkins PJ, Spruill S, Broadwater G, Vredenburgh JJ, Colvin OM, et al. Association between drug metabolism genotype, chemotherapy pharmacokinetics and overall survival in patient with breast cancer. J Clin Oncol 2005;23:6117–6125.

    Article  PubMed  CAS  Google Scholar 

  9. Yang G, Shu X-O, Ruan Z-X, Cai QY, Jin F, Gao Y-T, et al. Genetic polymorphism in glutathione-S-transferase genes (GSTM1, GSTT1, GSTP1) and survival after chemotherapy for invasive breast carcinomas. Cancer 2005;103:52–58.

    Article  PubMed  CAS  Google Scholar 

  10. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer J Clin Oncol 1998;16:2672–2685.

    PubMed  CAS  Google Scholar 

  11. Pierga JY, Mouret E, Laurence V, Diéras V, Savigioni A, Beuzeboc P, et al. Prognostic factors for survival after neoadjuvant chemotherapy in operable breast cancer. the role of clinical response Eur J Cancer 2003;39:1089–1096.

    Article  PubMed  Google Scholar 

  12. Lizard-Nacol S, Coudert B, Colosetti P, Riedinger J-M, Fargeot P, Brunet-Lecome P. Glutathione S transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer. Breast Cancer Res 1999;1:81–87.

    Article  PubMed  CAS  Google Scholar 

  13. Iwao-Koizumi K, Matoba R, Ueno N, Kim SJ, Ando A, Miyoshi Y, et al. Prediction of docetaxel response in human breast cancer by gene expression profiling. J Clin Oncol 2005;23:422–431.

    Article  PubMed  CAS  Google Scholar 

  14. Therasse P, Arbuc SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92:205–216.

    Article  PubMed  CAS  Google Scholar 

  15. Bell DA, Taylor JA, Paulson DF, Robertson CN, Mohler JL, Lucier GW. Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolic gene glutathione-S-transferase M1 (GSTM1) that increases the susceptibility to bladder cancer. J Natl Cancer Inst 1993;85:1159–1164.

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  17. Helzlsouer KJ, Selmin O, Huang HY, Strickland PT, Hoffman S, Alberg AJ, et al. Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J Natl Cancer Inst 1998;90:512–518.

    Article  PubMed  CAS  Google Scholar 

  18. Board PG. Gene deletion and partial deficiency of the glutathione S-transferase (ligandin) system in man. FEBS Lett 1981;135:2–4.

    Article  Google Scholar 

  19. Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, et al. Human glutathione-S-transferase (GSTT1) cDNA cloning and the characterization of a genetic polymorphism. Biochem J 1994;300:271–276.

    PubMed  CAS  Google Scholar 

  20. Hayes JD, Pulford DJ. The glutathione-S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 1995;30:445–600.

    Article  PubMed  CAS  Google Scholar 

  21. Mishra DK, Kumar A, Srivastava DS, Mittal RD. Allelic variation of GSTT1, GSTM1 and GSTP1 genes in North Indian population. Asian Pac J Cancer Prev 2004;5:362–365.

    PubMed  Google Scholar 

  22. Vettriselvi V, Vijayalakshmi K, Paul SF, Venkatachalam P. Genetic variation of GSTT 1, GSTM1 and GSTP1 genes in a South Indian population Asian Pac J Cancer Prev 2006;7:325–328.

    Google Scholar 

  23. Syamala VS, Sreeja L, Syamala V, Raveendran PB, Balakrishnan R, Kuttan R, et al. Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus sporadic breast cancer susceptibility and survival. Fam Cancer 2008;7:213–220.

    Article  PubMed  CAS  Google Scholar 

  24. Bai F, Nakanishi Y, Kawasaki M, Takayama K, Yatsunami J, Pei XH, et al. Immunohistochemical expression of glutathione S-transferase-Pi can predict chemotherapy response in patients with nonsmall cell lung carcinoma. Cancer 1996 1;78:416–421.

    Article  Google Scholar 

  25. Shiga H, Heath EI, Rasmussen AA, Trock B, Johnston PG, Forastiere AA, et al. Prognostic value of p53, glutathione S-transferase pi, and thymidylate synthase for neoadjuvant cisplatin-based chemotherapy in head and neck cancer. Clin Cancer Res 1999;5:4097–4104.

    PubMed  CAS  Google Scholar 

  26. Kusama M, Kubota T, Matsukura Y, Matsuno K, Ogawa S, Kanda Y, et al. Influence of glutathione S-transferase A1 polymorphism on the pharmacokinetics of busulfan. Clin Chim Acta 2006;368:93–98.

    Article  PubMed  CAS  Google Scholar 

  27. Mossallam GI, Abdel Hamid TM, Samra MA. Glutathione S-transferase GSTM1 and GSTT1 polymorphisms in adult acute myeloid leukemia; its impact on toxicity and response to chemotherapy. J Egypt Natl Cancer Inst 2006;18:264–273.

    Google Scholar 

  28. Barahmani N, Carpentieri S, Li XN, Wang T, Cao Y, Howe L, et al. Glutathione S-transferase M1 and T1 polymorphisms may predict adverse effects after therapy in children with medulloblastoma. NeuroOncology 2009;11:292–300.

    CAS  Google Scholar 

  29. Oldenburg J, Kraggerud SM, Brydøy M, Cvancarova M, Lothe RA, Fossa SD. Association between long-term neuro-toxicities in testicular cancer survivors and polymorphisms in glutathione-stransferase-P1 and -M1, a retrospective cross sectional study. J Transl Med 2007;5:70.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mishra, A., Chandra, R., Mehrotra, P.K. et al. Glutathione S-transferase M1 and T1 polymorphism and response to neoadjuvant chemotherapy (CAF) in breast cancer patients. Surg Today 41, 471–476 (2011). https://doi.org/10.1007/s00595-009-4310-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-009-4310-4

Key words

Navigation