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. 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.
Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil.
Gustavo J
GJ
Lourenço
Irene
I
Lorand-Metze
Marcia T
MT
Delamain
Eliana C M
EC
Miranda
Rodolfo
R
Kameo
Konradin
K
Metze
Carmen S P
CS
Lima
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1