Gene dose effects of GSTM1, GSTT1 and GSTP1 polymorphisms on outcome in childhood acute lymphoblastic leukemia
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Gene dose effects of GSTM1, GSTT1 and GSTP1 polymorphisms on outcome in childhood acute lymphoblastic leukemia. / Borst, Louise; Buchard, Anders; Rosthøj, Susanne; Wesolowska, Agata; Wehner, Peder Skov; Wesenberg, Finn; Dalhoff, Kim; Schmiegelow, Kjeld.
In: Pediatric Hematology & Oncology, Vol. 34, No. 1, 2012, p. 38-42.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Gene dose effects of GSTM1, GSTT1 and GSTP1 polymorphisms on outcome in childhood acute lymphoblastic leukemia
AU - Borst, Louise
AU - Buchard, Anders
AU - Rosthøj, Susanne
AU - Wesolowska, Agata
AU - Wehner, Peder Skov
AU - Wesenberg, Finn
AU - Dalhoff, Kim
AU - Schmiegelow, Kjeld
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Adolescent
KW - Child
KW - Child, Preschool
KW - Female
KW - Gene Dosage
KW - Glutathione S-Transferase pi
KW - Glutathione Transferase
KW - Humans
KW - Infant
KW - Male
KW - Polymorphism, Genetic
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma
U2 - 10.1097/MPH.0b013e3182346cdd
DO - 10.1097/MPH.0b013e3182346cdd
M3 - Journal article
C2 - 22215096
VL - 34
SP - 38
EP - 42
JO - European Paediatric Haematology and Oncology
JF - European Paediatric Haematology and Oncology
SN - 0888-0018
IS - 1
ER -
ID: 38258175