Gene Dose Effects of GSTM1, GSTT1 and GSTP1 Polymorphisms on Outcome in Childhood Acute Lymphoblastic Leukemia

Publication: Research - peer-reviewJournal article – Annual report year: 2012

  • Author: Borst, Louise

    University Hospital Rigshospitalet, Juliane Marie Centre

  • Author: Buchard, Anders

    University of Copenhagen, Section of Forensic Genetics

  • Author: Rosthoj, Susanne

    University of Copenhagen, Department of Biostatistics

  • Author: Wesolowska, Agata

    Department of Systems Biology, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Wehner, Peder Skov

    Odense University Hospital, H. C. Andersen Children’s Hospital

  • Author: Wesenberg, Finn

    National Hospital, Oslo, Department of Pediatrics

  • Author: Dalhoff, Kim

    Bispebjerg Hospital, Department of Clinical Pharmacology

  • Author: Schmiegelow, Kjeld

    University of Copenhagen, Faculty of Health Sciences

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Children with acute lymphoblastic leukemia (ALL) react very differently to chemotherapy. One explanation for this is inherited genetic variation. The glutathione S-transferase (GST) enzymes inactivate a number of chemotherapeutic drugs administered in childhood ALL therapy. Two multiplexing methods were applied for genotyping the GSTM1 and GSTT1 genes (distinguishing between 0, 1, or 2 gene copies) and the GSTP1 313 A>G polymorphism, simultaneously. A total of 263 childhood ALL patients were genotyped. No gene dose effect on outcome was demonstrated with either GST polymorphisms. Grouping of GSTM1 and GSTT1 into poor (0 or 1 gene copy)-and good metabolizers (at least 2 gene copies)-showed that the poor metabolizers had a trend toward a better outcome (event-free survival = 91.8%) compared with the good metabolizers (event-free survival = 83.2%). Similarly, in the adjusted analysis the good metabolizers demonstrated a 2.2-fold higher risk trend of experiencing an event (resistant disease or relapse) compared with the poor metabolizers (P = 0.066; hazard ratio = 2.248; 95% confidence interval, 0.948-5.327). In conclusion, our results suggest that the combined gene dose of GSTM1 and GSTT1 may influence outcome in childhood ALL.
Original languageEnglish
JournalJournal of Pediatric Hematology / Oncology
Publication date2012
Volume34
Journal number1
Pages38-42
ISSN1077-4114
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 6

Keywords

  • Gene dose effect, Childhood acute lymphoblastic leukemia, Genetic polymorphism, Outcome, Glutathione S-transferase
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