Role of glutathione-s-transferase and CYP1A1*2A polymorphisms in the therapy outcome of south Indian acute lymphoblastic leukemia patients

Autor: Suneetha, K. J., Nancy, K. Nirmala, Rajalekshmy, K. R., Rama, R., Sagar, T. G., Rajkumar, T.
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: Indian Journal of Medical and Paediatric Oncology : Official Journal of Indian Society of Medical & Paediatric Oncology
ISSN: 0975-2129
0971-5851
Popis: Background: Polymorphisms in the drug-metabolizing enzymes are found to be associated with the inter-individual variation in response to a particular drug. Glutathione S-transferases (GSTs) are involved in the metabolism of several anticancer drugs, including alkylating agents, anthracyclines, and cyclophosphamides. Aim: The present study is aimed to examine the association of GST and CYP1A1*2A polymorphisms in the susceptibility to acute lymphoblastic leukemia (ALL) and the prognostic significance. Materials and Methods: A total of 92 immunophenotyped patients and 150 cord blood controls were genotyped by PCR for GSTM1 and GSTT1, RQ-PCR allelic discrimination assay for GSTP1 and PCR-RFLP for CYP1A1*2A polymorphism. Results: We have previously reported the significant association of GSTM1 (null) and combined GSTP1 {(Ile/Val)/ (Val/Val)} /GSTM1 (null) genotype with the susceptibility to ALL. No significant association was observed with GSTT1 (P=0.75) and CYP1A1*2A (P=0.61 for +/- and P=0.86 for -/- respectively) in the susceptibility to ALL. Survival analysis was performed in 50 of the 92 patients who were followed for three years. Kaplan-Meier survival analysis for three years showed significant lower event-free survival in patients harboring GSTP1 (Ile/Val) and GSTP1 (Val/Val) (P=0.038 and 0.0001, respectively) genotype. Cox regression analysis revealed GSTP1 as an independent prognostic marker with 6-fold higher risk with Val/Val genotype (P=0.003). Conclusions: Our results show that GSTP1 (Ile/Val) polymorphism has a role in the susceptibility to ALL and also influence treatment outcome.
Databáze: OpenAIRE
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