title: Clinical implications of glutathione S-transferase genotyping in patients with diffuse large B-cell lymphoma.
abstract: OBJECTIVE
  Polymorphic deletions in glutathione S-transferase (GST) genes are recognized as a risk factor for lymphoma, other hematological and non-hematological malignancies. The purpose of the present study was to investigate whether deletions of GSTT1 and GSTM1 as well as GSTP1 Ile- 105Val single nucleotide polymorphism influence clinical presentation, response to therapy and outcome in patients with diffuse large B-cell lymphoma (DLBCL).
  
  
  METHODS
  The study included a total of 82 DLBCL patients treated with rituximab-CHOP (R-CHOP) therapy (6-8 cycles). GST genes were analyzed with PCR-based methodology.
  
  
  RESULTS
  The obtained frequencies of GSTT1 and GSTM1 null genotypes were 24 and 63%, respectively. The variant GSTP1 Val allele was present in 76% of the patients. No association between GST genotypes and clinical presentation was found. However, a higher frequency of GSTM1 null genotype was observed in patients who developed DLBCL before the age of 60 [odds ratio (OR) 3.12, 95% confidence interval (CI) 1.11-9.17; p=0.03]. Patients carrying at least one GSTP1 Val allele achieved remission in a shorter time period than patients with GSTP1 Ile/Ile genotype (p=0.05). GST genotypes didn't influence the incidence of relapse and survival. There were no toxic effects, life-threatening infections or significant delay in immunochemotherapy in the analyzed group of patients.
  
  
  CONCLUSIONS
  The present study showed the association of GSTM1 null genotype and DLBCL development before the age of 60 (prognostic cutoff). GST genotypes didn't influence survival, but patients with at least one low-producing GSTP1 Val allele achieved clinical remission in a shorter time period.
authors.affiliation: Clinic for Hematology, Military Medical Academy, Belgrade, Serbia.
authors.forename: Lavinika
authors.initials: L
authors.lastname: Atanaskovic
authors.forename: Bojana
authors.initials: B
authors.lastname: Cikota-Aleksic
authors.forename: Olivera
authors.initials: O
authors.lastname: Tarabar
authors.forename: Jovana
authors.initials: J
authors.lastname: Trimcev
authors.forename: Andelina
authors.initials: A
authors.lastname: Zivanovic-Ivic
authors.forename: Slobodan
authors.initials: S
authors.lastname: Marjanovic
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Magic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D055771:Serbia; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human