Polymorphisms within glutathione S-transferase genes in pediatric non-Hodgkin's lymphoma.
OBJECTIVE
Glutathione S-transferases (GSTs) are involved in the metabolism of a number of cancer chemotherapeutic agents. Certain members within the GST superfamily exhibit phenotypically relevant genetic polymorphisms which have been associated with outcome in hematologic malignant disease.


METHODS
In the present study we genotyped a cohort of 169 pediatric non-Hodgkin's lymphoma (NHL) patients with available specimens from the NHL-BFM trials 86 and 90 conducted by the Berlin-Frankfurt-Münster (BFM) study group to assess a potential association of phenotypically relevant glutathione S-transferase polymorphisms (GSTM1, GSTT1, GSTP1 codon 105) with treatment outcome in this patient group.


RESULTS
Treatment failure in patients with mature B-cell NHL was significantly less likely to occur in patients carrying at least one GSTM1 allele in comparison to those with a homozygous deletion of GSTM1. This protective effect mediated by the presence of GSTM1 was even more pronounced within the subset of therapy group B patients at highest clinical risk of treatment failure (B-ALL, disease stage IV, disease stage III with unresected abdominal tumor, and LDH activity > or = 500 U/L). Of all events in therapy group B, 87.5% occurred in this high risk group. Within this subset, the multivariate relative risk reached 4.98 (95% CI = 1.27-19.52; p= 0.021).


CONCLUSIONS
Our results suggest that genetic variation at the GSTM1 locus may be of clinical importance in pediatric NHL and may be a potential candidate for indicating future treatment stratification strategies.
Dieckvoss
Björn-Ole
BO
Department of Pediatric Hematology and Oncology, Children s Hospital, Hannover Medical School, Hannover, Germany.
Stanulla
Martin
M
Schrappe
Martin
M
Beier
Rita
R
Zimmermann
Martin
M
Welte
Karl
K
Reiter
Alfred
A
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007527:Isoenzymes / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D008297:Male; D011110:Polymorphism, Genetic; D011379:Prognosis; D017211:Treatment Failure
D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase