Polymorphisms of glutathione S-transferase mu 1, theta 1, and pi 1 genes and prognosis in Hodgkin lymphoma

We examined the influence of the glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1), and pi 1 (GSTP1) polymorphisms, which are involved in the metabolism of alkylating agents and anthracyclines, on the outcome of patients with Hodgkin lymphoma (HL) treated with conventional chemotherapy. Genomi...

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Bibliographic Details
Published in:Leukemia & lymphoma 2010-12, Vol.51 (12), p.2215-2221
Main Authors: Lourenço, Gustavo J., Lorand-Metze, Irene, Delamain, Marcia T., Miranda, Eliana C. M., Kameo, Rodolfo, Metze, Konradin, Lima, Carmen S. P.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Female
Genotype
Glutathione S-Transferase pi - genetics
Glutathione Transferase - genetics
GSTM1
GSTP1
GSTT1
Hodgkin Disease - diagnosis
Hodgkin Disease - genetics
Hodgkin Disease - mortality
Hodgkin lymphoma
Humans
Male
Middle Aged
Polymorphism, Genetic
Prognosis
Retrospective Studies
Survival Analysis
Young Adult
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Summary:We examined the influence of the glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1), and pi 1 (GSTP1) polymorphisms, which are involved in the metabolism of alkylating agents and anthracyclines, on the outcome of patients with Hodgkin lymphoma (HL) treated with conventional chemotherapy. Genomic DNA from 125 consecutive cases was analyzed by polymerase chain reaction and enzymatic digestion for polymorphism determination. The GSTM1 undeleted genotype was associated with more advanced tumor stage and worse disease-free survival. The GSTT1 undeleted genotype was associated with higher recurrence rate. In contrast, higher toxicity of chemotherapy was attributed to absence of the GSTT1 gene. Concerning overall survival, lower tumor stage (p = 0.006) and International Prognostic Score (p = 0.02), lower peripheral leukocyte count (p = 0.0003), higher serum albumin level (p = 0.08), and GSTT1 undeleted genotype (p = 0.04) were predictive of a better outcome of patients. In multivariate analysis comparing staging and GST polymorphism, only tumor stage and GSTT1 genotype remained in the model. Our results suggest that the GSTT1 polymorphism influences the outcome of Brazilian patients with HL. However, studies of toxicity, pharmacokinetics, and protein function may clarify whether carriers of the distinct genotypes should receive different doses of chemotherapeutic agents.
ISSN:1042-8194
1029-2403
DOI:10.3109/10428194.2010.527402