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

Louise Borst, Anders Buchard, Susanne Rosthoj, Agata Wesolowska, Peder Skov Wehner, Finn Wesenberg, Kim Dalhoff, Kjeld Schmiegelow

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    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
    Volume34
    Issue number1
    Pages (from-to)38-42
    ISSN1077-4114
    DOIs
    Publication statusPublished - 2012

    Keywords

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

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