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

Authors: Cho, HJ  Eom, HS  Kim, HJ  Kim, IS  Lee, GW  Kong, SY 
Citation: Cho HJ, etal., Cancer Genet Cytogenet. 2010 Apr 1;198(1):40-6. doi: 10.1016/j.cancergencyto.2009.12.004.
Pubmed: (View Article at PubMed) PMID:20303013
DOI: Full-text: DOI:10.1016/j.cancergencyto.2009.12.004

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 genotyped 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% CI, 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% CI, 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.


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CRRD Object Information
CRRD ID: 10450835
Created: 2016-01-21
Species: All species
Last Modified: 2016-01-21
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.