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 language | English |
|---|---|
| Journal | Pediatric Hematology & Oncology |
| Volume | 34 |
| Issue number | 1 |
| Pages (from-to) | 38-42 |
| Number of pages | 5 |
| ISSN | 0888-0018 |
| DOIs | |
| Publication status | Published - Jan 2012 |
Keywords
- Adolescent
- Child
- Child, Preschool
- Female
- Gene Dosage
- Glutathione S-Transferase pi
- Glutathione Transferase
- Humans
- Infant
- Male
- Polymorphism, Genetic
- Precursor Cell Lymphoblastic Leukemia-Lymphoma