Polymorphisms within glutathione S-transferase genes in pediatric non-Hodgkin's lymphoma

Abstract

BACKGROUND AND OBJECTIVES: 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. DESIGN AND 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-Munster (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). INTERPRETATION AND 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.