engleski

GSTP1 ILE105VAL POLYMORPHISM AND DOXORUBICIN INDUCED TOXICITY IN CHILDREN WITH SOLID TUMORS

Purpose: Doxorubicin is an anthracycline antibiotic with antineoplastic activity. It is used against a wide spectrum of human cancers but it can induce a dose-dependent cardiotoxicity. Glutathion S-transferase P (GSTP) plays a role in detoxification process of some chemotherapy agents including anthracyclines. GSTP1 Ile105Val substitution lies within the substrate-binding site and it was reported to be associated with altered catalytic activity of the enzyme. The aim of our study was to evaluate the correlation between GSTP1 105 polymorphism and doxorubicin induced cardiotoxicity and hematotoxicity in children with solid tumors in Croatian population. Method: Our study was performed on 46 children with solid tumors treated in Children's Hospital Zagreb. All patients received doxorubicin chemotherapy. Toxicity was assessed according to the NCI Common toxicity criteria (version 2.0). The study was approved by the Ethics Committee of the Children's Hospital Zagreb. GSTP1 polymorphism was analyzed using predeveloped real-time PCR Taqman® SNP genotyping assay. Results: Higher occurence of cardiotoxicity and hematotoxicity grade 3 were noticed in carriers of GSTP1 minor allele -313G (AG and GG genotypes). Conclusion: This finding supports the thesis that GSTP1 105 SNP alters the catalytic efficacy of GSTP1 and thus can cause severe toxicities to the patient. These results are a part of prospective pharmacogenetic study of correlation of polymorphisms in genes regulating chemotherapeutic metabolism and chemotherapy used for treatment of children with solid tumours in Croatian population. We hope that the results of this project will be used for improvement of antitumour therapy in affected children.

doxorubicin; GSTP; cardiotoxicity; children

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