Glutathione-S-transferase genotypes influence the risk of chemotherapy-related toxicities and prognosis in Korean patients with diffuse large B-cell lymphoma

Abstract

Polymorphisms in detoxification enzymes of the glutathione S-transferase (GST) family are associated with treatment response, resistance, and drug-related toxicity, all of which affect final clinical outcome. In this study, we investigated the influence of the genetic polymorphisms GSTM1, GSTT1, and GSTP1 on treatment response in 94 Korean patients with de novo diffuse large B-cell lymphoma, who had received rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) as a front-line regimen. Deletions of the GSTM1 and GSTT1 genes were detected using a multiplex polymerase chain reaction technique, and the functional GSTP1 polymorphism, Ile(105)Val, was geno-typed using the TaqMan assay. The treatment response rate did not differ according to GST polymorphisms. Patients with the GSTT1-null genotype, however, showed more frequent grade III-IV chemotherapy-related toxicities, including leukocytopenia [odds ratio (OR) = 3.1; 95% confidence interval (95%CI), 1.2-8.0; P = 0.025], fever (OR = 5.3; 95% Cl, 1.4-19.7; P = 0.009), and mucositis (OR = 4.6; 95% CI, 1.4-15.1; P = 0.012). Patients with the GSTM1/T1 double-null genotype had more grade III-IV thrombocytopenia (OR = 7.8; 95% Cl, 1.5-41.1; P = 0.002) compared to those with other genotypes. In male patients, the GSTM1/T1 double-null genotype was associated with a shorter event-free survival period (P = 0.02). This study suggests that GSTT1 deletion may significantly increase the risk of drug-related toxicity after R-CHOP chemotherapy in patients with DLBCL, and is associated with worse prognosis in males. (C) 2010 Elsevier Inc. All rights reserved.