THE EFFECT OF POLYMORPHISM IN GLUTATHIONE S-TRANSFERASES ON THE DEVELOPING SECOND MALIGNANT NEOPLASMS AFTER LEUKEMIA TREATMENT IN CHILDHOOD

  • Janez Jazbec Služba za onkologijo in hematologijo Pediatrična klinika Klinični Center Vrazov trg 1 1525 Ljubljana
  • Vita Dolžan Inštitut za biokemijo Medicinska fakulteta v Ljubljani Vrazov trg 2 1000 Ljubljana
  • Maruša Debeljak Služba za onkologijo in hematologijo Pediatrična klinika Klinični Center Vrazov trg 1 1525 Ljubljana
  • Richard Aplenc Children’s Hospital of Philadelphia 34th Street Philadelphia USA
  • Berta Jereb Onkološki inštitut Ljubljana Zaloška 2 1000 Ljubljana
Keywords: gluthatione S-transferase, childhood leukemia, secondary neoplasm

Abstract

Background. Survivors of childhood leukemia have an increased risk of developing second malignant neoplasms and specific treatment factors such as alkylating agents, topoisomerase inhibitors and radiation have been associated with their occurrence. Genetic polymorphism in drug-metabolizing enzymes may result in impared detoxification of chemotherapeutics and may lead to increased risk for cancer.

Methods. To test if polymorphism in glutathione S-transferases (GST) genes is associated with occurrence of secondary malignant neoplasms, we compared GSTM1, GSTT1 and GSTP1 genotypes among 16 patients treated for childhood leukemia in whom second neoplasm occurred and matched the control group.

Results. GSTM1 null genotype was found in 44% of patients with second neoplasms and in 50% in control group (p = 0.768), GSTT1 null genotype in 19% of cases and in 29% of controls (p = 0.729) and GSTP1 105 Ile/ile in 50% of cases and 37% of controls (p = 0.537). Differences in distribution of GST genotypes in patients with second neoplasms after childhood leukemia, compared to a matched control group of patients were not statistically significant.

Conclusions. In our study we were not able to show relation between GST genotype and occurrence of second neoplasms after the childhood acute leukemia.

Downloads

Download data is not yet available.

References

Bhatia S, Buckley J, Robinson L. Second malignancies in childhood cancer. CCG Quarterly 1997; 5: 8–23.

Inocenti F, Iyer L, Ratain MJ. Pharmacogenetics. A tool for individualizing antineoplastic therapy. Clin Pharmacokinet 2000; 39: 315–25.

Morel F, Rauch C, Coles B, Le Ferrec E, Guillouzo A. The human glutathione transferase alpha locus: genomic organization of the gene cluster and functional characterization of the genetic polymorphism in the hGSTA1 promoter. Pharmacogenetics 2002; 12: 277–86.

Rebbeck TR. Molecular epidemiology of the human glutathione Stransferase GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 1997; 6: 733–43.

Elexpuru-Camiruaga J, Buxton M, Kandula V et al. Susceptibility to astrocitoma and meningioma: influence of allelism at glutathione S-transferase (GSTM1 and GSTT1) and cytochrome P-450 (CYP2D6) loci. Cancer research 1995; 55: 4237–9.

Hengstler JG, Arand M, Herrero ME, Oesch F. Polymorphism of Nacetyltransferase, glutathion S-transferase, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. Recent Results Cancer Research 1998; 154: 47–85.

Rebbeck TR. Mollecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 1997; 6: 733–43.

Strange RC, Lear JT, Fryer AA. Polymorphism in glutathione S-transferase loci as a risk factor for common cancers. Arch Toxicol 1998; 72: Suppl: 419–28.

Allan JM, Wild CP, Rollinson S, Wilett EV, Moorman AV, Dovey GJ, Roddam PL, Roman E, Cartwright RA, Morgan GJ. Polymorphism in glutathion S-transferase P1 is associated with succeptibility to chemotherapy induced leukemia. PNAS 2001; 98: 11592–7.

Rosario LA, O’Brien ML, Henderson CJ, Wolf CR, Tew KD. Cellular response to a glutathione S-transferase P1 activated prodrug. Molecular Pharmacology 2000; 58: 167–74.

Ishimoto TI, Ali-Osman F. Allelic variants of the human glutathione S-transferase P1 gene confer differential cytoprotection against anticancer agents in Escherichia coli. Pharmacogenetics 2002; 12: 543–53.

Standulla M, Schrape M, Mueller-Brechlin A, Zimmermann M, Welte K. Polymorphism within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukaemia: a case-control study. Blood 2000; 95: 1222–8.

Aplenc R, Orudjev E, Swoyer J, Manke B, Rebbeck T. Differential bone marrow aspirate DNA yields from commercial extraction kits. Leukemia 2002; 16: 1865–6.

Chen CL, Liu Q, Relling ML. Simultaneous characterization of glutathione Stransferase M1 and T1 polymorphism by polymerase chain reaction in American whites and blacks. Pharmacogenetics 1996, 6: 187–91.

Ali-Osman F, Akande O, Antoun G, Mao JX, Buolamwin J. Molecular cloning, characterization and expression in Escherichia coli of full length cDNAs of three human glutathione S-transferase Pi gene variants. J Biol Chem 1997, 272: 10004–12.

Chen CL, Liu Q, Pui CH, Rivera GK, Sandlund JT, Riberiro R, Evans WE, Relling MV. Higher frequency of glutathione S-transferase deletions in black children with acute lymphoblastic leukemia. Blood 1997; 89: 1701–7.

Nelson HH, Wiencke JK,, Christiani DC, Cheng TJ, Zuo ZF, Schwartz BS, Lee BK, Spitz MR, Wang M, Xu X. Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta. Carcinogenesis 1995; 16: 1243–5.

Woo MH, Shuster JJ, Chen C, Bash RO, Behm FG, Camitta B, Felix CA, Kamen BA, Pui CH, Raimondi SC, Winick NJ, Amylon MD, Relling MV. Glutathione Stransferase genotypes in children who develop treatment-related acute myeloid leukemia. Leukemia 2000; 14: 232–7.

Crump C, Chen C, Appelbaum FR et al. Glutathione S-transferase Theta 1 gene deletion and risk of acute myeloid leukemia. Cancer Epidemiology, Biomarkers & Prevention 2000; 9: 457–60.

Haase D, Binder C, Bunger J et al. Increased risk for therapy-induced hematologic malignancies in patients with carcinoma of the breast and combined homozygous gene deletions of glutathione transferases M1 and T1.Leukemia Research 2002; 26: 249–54.

How to Cite
1.
Jazbec J, Dolžan V, Debeljak M, Aplenc R, Jereb B. THE EFFECT OF POLYMORPHISM IN GLUTATHIONE S-TRANSFERASES ON THE DEVELOPING SECOND MALIGNANT NEOPLASMS AFTER LEUKEMIA TREATMENT IN CHILDHOOD. TEST ZdravVestn [Internet]. 1 [cited 5Aug.2024];73. Available from: http://vestnik-dev.szd.si/index.php/ZdravVest/article/view/2416
Section
Professional Article