Impact of single nucleotide polymorphisms of cytarabine metabolic genes on drug toxicity in childhood acute lymphoblastic leukemia

BACKGROUND: Cytarabine (cytosine arabinoside, ara-C) is a chemotherapeutical agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL). Adverse drug reactions, such as interpatient variability in sensitivity to ara-C, are considerable and may cause difficulties during chemotherapy....

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Elmentve itt :
Bibliográfiai részletek
Szerzők: Gábor Krisztina
Schermann Géza
Lautner-Csorba Orsolya
Rárosi Ferenc
Erdélyi Dániel
Börcsökné Endreffy Emőke
Berek Krisztina
Bartyik Katalin
Bereczki Csaba
Szalai Csaba
Semsei Ágnes F.
Dokumentumtípus: Cikk
Megjelent: 2015
Sorozat:PEDIATRIC BLOOD & CANCER 62 No. 4
doi:10.1002/pbc.25379

mtmt:2807591
Online Access:http://publicatio.bibl.u-szeged.hu/11920
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245 1 0 |a Impact of single nucleotide polymorphisms of cytarabine metabolic genes on drug toxicity in childhood acute lymphoblastic leukemia  |h [elektronikus dokumentum] /  |c  Gábor Krisztina 
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520 3 |a BACKGROUND: Cytarabine (cytosine arabinoside, ara-C) is a chemotherapeutical agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL). Adverse drug reactions, such as interpatient variability in sensitivity to ara-C, are considerable and may cause difficulties during chemotherapy. Single nucleotide polymorphisms (SNPs) can play a significant role in modifying nucleoside-drug pharmacokinetics and pharmacodynamics and thus the development of adverse effects. Our aim was to determine whether polymorphisms in genes encoding transporters and enzymes responsible for the metabolism of ara-C are associated with toxicity and clinical outcome in a patient population with childhood ALL. PROCEDURE: We studied 8 SNPs in the CDA, DCK, DCTD, SLC28A3, and SLC29A1 genes in 144 patients with childhood acute lymphoblastic leukemia treated according to ALLIC BFM 1990, 1995 and 2002 protocols. RESULTS: DCK rs12648166 and DCK rs4694362 SNPs were associated with hematologic toxicity (OR = 2.63, CI 95% = 1.37-5.04, P = 0.0036 and OR = 2.53, CI 95% = 1.34-4.80, P = 0.0044, respectively). CONCLUSIONS: Our results indicate that DCK polymorphisms might be important genetic risk factors for hematologic toxicity during ALL treatment with ara-C. Individualized chemotherapy based on genetic profiling may help to optimize ara-C dosing, leading to improvements in clinical outcome and reduced toxicity. Pediatr Blood Cancer 2014;9999:1-7(c) 2015 Wiley Periodicals, Inc. 
700 0 1 |a Schermann Géza  |e aut 
700 0 2 |a Lautner-Csorba Orsolya  |e aut 
700 0 2 |a Rárosi Ferenc  |e aut 
700 0 2 |a Erdélyi Dániel  |e aut 
700 0 2 |a Börcsökné Endreffy Emőke  |e aut 
700 0 2 |a Berek Krisztina  |e aut 
700 0 2 |a Bartyik Katalin  |e aut 
700 0 2 |a Bereczki Csaba  |e aut 
700 0 2 |a Szalai Csaba  |e aut 
700 0 2 |a Semsei Ágnes F.  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/11920/1/O_Impact_of_SNPS_of_Cytarabine_metabolic_genes_2015_Gabor_u.pdf  |z Dokumentum-elérés