Skip to main content

Advertisement

Log in

GSTM1 and codon 72 P53 polymorphism in multiple myeloma

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

The GSTM1 and GSTT1 genes reduce the effects of exposure to cytotoxic agents. Both genes have a null variant allele in which the entire gene is absent. On the other hand, a common polymorphism of the tumour suppressor P53 gene results in either arginine (A) or proline (P) at amino-acid position 72. The A and P alleles code proteins with distinct functions in apoptosis and DNA repair and have been associated with variable risks for several cancers. However, their roles in multiple myeloma (MM) are still unknown. We tested in study whether the GSTM1, GSTT1 and P53 genotypes altered the risk for MM in Brazilian patients. Genomic DNA from 106 patients and 230 controls were analysed by polymerase chain reaction-based methods for identification of the genotypes. Similar frequencies of the GSTM1, GSTT1 and P53 genotypes were seen in patients and controls. Individuals with the distinct genotypes had similar risks for disease. In contrast, an excess of the GSTM1 null (45.1 vs 17.2%, P = 0.009), the P53 PP+AP (70.4 vs 44.8%, P = 0.041) and the GSTM1 null plus P53 PP+AP (29.6 vs 10.3%, P = 0.004) genotypes were seen in MM patients at stage III compared with those at stages I + II. Our data suggest that the GSTM1, GSTT1 and P53 genotypes do not influence the risk for MM. However, the inherited presence of the variant codon 72 P53 allele, described here for the first time, and the absence of the GSTM1 detoxification pathway, seem to act in disease progression in our country.

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.

Fig. 1

Similar content being viewed by others

References

  1. Morris PD, Koepsell TD, Daling JR (1986) Toxic substance exposure and multiple myeloma. A case-control study. J Natl Cancer Inst 76:987–992

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  3. Hengstler JG, Arand M, Herrero ME, Oesh F (1998) Polymorphisms of N-acetyl-transferases, glutathione S-transferase, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. Recent Results Cancer Res 154:47–85

    PubMed  CAS  Google Scholar 

  4. Chen H, Sandler DP, Taylor JA, Shore DL, Liu E, Bloomfield CD et al (1996) Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1 (GSTT1) gene defect. Lancet 347:295–297

    Article  PubMed  CAS  Google Scholar 

  5. Davies SM, Robison LL, Buckley JD, Radloff GA, Ross JA, Perentesis JP (2000) Glutathione S-transferase polymorphisms in children with myeloid leukemia: a children’s cancer group study. Cancer Epidemiol Biomarkers Prev 9:563–566

    PubMed  CAS  Google Scholar 

  6. Arruda VR, Lima CSP, Grignoli CRE, Melo MB, Lorand-Metze I, Alberto FL et al (2001) Increased risk for acute myeloid leukaemia in individuals with glutathione S-transferase Mu 1 (GSTM1) and Tetha 1 (GSTT1) gene Defects. Eur J Haematol 66:383–388

    Article  PubMed  CAS  Google Scholar 

  7. Ye Z, Song H (2005) Glutathione S-transferase polymorphisms (GSTM1, GSTP1 and GSTT1) and the risk of acute leukaemia: a systematic review and meta-analysis. Eur J Cancer 41:980–989

    Article  PubMed  CAS  Google Scholar 

  8. Ortega MM, Nascimento H, Melo MB, Teori MT, Costa FF, Lima CSP (2003) Polymorphisms of glutathione S-transferase mu1 (GSTM1) and theta 1 (GSTT1) genes in multiple myeloma. Acta Haematol 109:108–109

    Article  PubMed  Google Scholar 

  9. Lincz LF, Kerridge I, Scorgie FE, Bailey M, Enno A, Spencer A (2004) Xenobiotic gene polymorphisms and susceptibility to multiple myeloma. Haematologica 89:628–629

    PubMed  CAS  Google Scholar 

  10. Ara S, Lee PS, Hansen MF, Saya H (1990) Codon 72 polymorphism of the TP53 gene. Nucleic Acids Res 18:4961–4968

    Article  PubMed  CAS  Google Scholar 

  11. Frebourg T, Friend SH (1993) The importance of the p53 gene alterations in human cancer: is there more than circumstantial evidence? J Natl Cancer Inst 85:1554–1557

    Article  PubMed  CAS  Google Scholar 

  12. Dumont P, Leu JL, Della Pietra AC, George DL, Murphy M (2003) The codon 72 polymorphism variants of p53 have markedly different apoptotic potential. Nat Genet 33:357–365

    Article  PubMed  CAS  Google Scholar 

  13. Siddique M, Sabapathy K (2006) Trp53-dependent DNA-repair is affected by the codon 72 polymorphism. Oncogene 25:3489–3500

    Article  PubMed  CAS  Google Scholar 

  14. Sjalander A, Birgander R, Athlin L, Stenling R, Rutegard J, Beckman L et al (1995) P53 germ line haplotypes associated with increased risk for colorectal cancer. Carcinogenesis 16:1461–1464

    Article  PubMed  CAS  Google Scholar 

  15. Weston A, Godbold JH (1997) Polymorphisms of the H-ras and p53 in breast cancer and lung cancer: a meta-analysis. Environ Health Perspect 105:919–926

    Article  PubMed  CAS  Google Scholar 

  16. Papadakis EN, Dokianakis DN, Spandidos DA (2000) P53 codon 72 polymorphism a as risk factor in the development of breast cancer. Mol Cell Res Commun 3:389–392

    Article  CAS  Google Scholar 

  17. Siddique MM, Balram C, Fiszer-Maliszewska L, Aggarwal A, Tan A, Tan P et al (2005) Evidence for selective expression of the p53 codon 72 polymorphisms: implications in cancer development. Cancer Epidemiol Biomarkers Prev 14:2245–2252

    Article  PubMed  CAS  Google Scholar 

  18. Jin X, Wu X, Roth JA, Amos CI, King TM, Branch C et al (1995) Higher lung cancer risk for younger African-Americans with the Pro/Pro p53 genotype. Carcinogenesis 16:2205–2208

    Article  PubMed  CAS  Google Scholar 

  19. Miller DP, Liu G, De Vivo I, Lynch TJ, Wain JC, Su L et al (2002) Combinations of the variant genotypes of GSTP1, GSTM1, and p53 are associated with an increased lung cancer risk. Cancer Res 62:2819–2823

    PubMed  CAS  Google Scholar 

  20. Granja F, Morari EC, Correa LAC, Assumpção LVM, Ward LS (2004) Proline homozygosity in codon 72 of p53 is a factor of susceptibility for thyroid cancer. Cancer Lett 210:151–157

    Article  PubMed  CAS  Google Scholar 

  21. Kalemi TG, Lambropoulos AF, Gueorguiev M, Chrisafi S, Papazisis KT, Kotsis A (2005) The association of p53 mutations and p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms with breast cancer in northern Greece. Cancer Lett 222:57–65

    Article  PubMed  CAS  Google Scholar 

  22. Ueda M, Hung Y-C, Terai Y, Saito J, Nunobiki O, Noda S et al (2005) Glutathione S-Transferase and p53 polymorphisms in cervical carcinogenesis. Gynecol Oncol 96:736–740

    Article  PubMed  CAS  Google Scholar 

  23. To-Figueras J, Gene M, Gomes-Catalan J, Galan C, Firvida J, Fuentes M et al (1996) Glutathione S-Transferase M1 and codon 72 p53 polymorphsims in a northwestern Mediterranean population and their relation to lung cancer susceptibility. Cancer Epidemiol Biomark Prev 1(5):337–342

    Google Scholar 

  24. Barlogie B, Shaughnessy J, Munshi N, Epstein J (2001) Plasma cell myeloma. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Selingson U (eds) Hematology. McGraw-Hill, New York, pp 1279–1304

    Google Scholar 

  25. Durie BGM, Salmon SE (1975) A clinical staging system for multiple myeloma. Cancer 36:842–854

    Article  PubMed  CAS  Google Scholar 

  26. Carvalho-Silva DR, Santos FR, Rocha J, Pena SD (2001) The phylogeography of Brazilian Y-chromosome lineages. Am J Hum Genet 68:281–286

    Article  PubMed  CAS  Google Scholar 

  27. Lorand IGH, Souza CA, Costa FF (1984) Haematological toxicity associated with agricultural chemicals in Brazil. Lancet 1:404

    Article  PubMed  CAS  Google Scholar 

  28. Shields PG (1993) Molecular epidemiology and the genetics of environmental cancer. J Am Med Assoc 266:681–687

    Article  Google Scholar 

  29. Ruiz MA, Augusto LGS, Vassallo J, Vigorito AC, Lorand-Metze I, Souza CA (1994) Bone marrow morphology in patients with neutropenia due to chronic exposure to organic solvents. Pathol Res Pract 190:151–154

    PubMed  CAS  Google Scholar 

  30. Augusto LGS, Lieber SR; Ruiz MA; Souza CA (1977) Micronucleus monitoring to assess human occupational exposure to organochlorides. Environ Mol Mutagen 29:46–52

    Article  Google Scholar 

  31. Queiroz MLS, Bincoleto C, Perlingeiro RCR, Souza CA, Toledo H (1997) Defective neutrophil function in workers occupationally exposed to hexachlorobenzene. Human Exp Toxicol 16:322–326

    Article  CAS  Google Scholar 

  32. Risinger MA, Groden J (2004) Crosslinks and crosstalk: human cancer syndromes and DNA repair deffects. Cancer Cell 6:539–545

    PubMed  CAS  Google Scholar 

  33. Sengupta S, Harris CC (2005) P53: traffic cop at the crossroads of DNA repair and recombination. Nat Rev Mol Cell Biol 6:44–55

    Article  PubMed  CAS  Google Scholar 

  34. Marchenko ND, Zalka A, Moll UM (2000) Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J Biol Chem 275:16202–16212

    Article  PubMed  CAS  Google Scholar 

  35. Takeuchi S, Matsushita M, Tsukasaki K, Takeuchi N, Tomonaga M, Komatsu N et al (2005) P53 codon 72 polymorphism is associated with disease progression in adult T-cell leukaemia/lymphoma. Br J Haematol 131:552–556

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are indebted to Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP) for financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carmen S. P. Lima.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ortega, M.M., Honma, H.N., Zambon, L. et al. GSTM1 and codon 72 P53 polymorphism in multiple myeloma. Ann Hematol 86, 815–819 (2007). https://doi.org/10.1007/s00277-007-0347-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-007-0347-x

Keywords

Navigation