Journal
PEDIATRIC BLOOD & CANCER
Volume 52, Issue 3, Pages 364-368Publisher
WILEY
DOI: 10.1002/pbc.21815
Keywords
DNA methylation; drug metabolism; homocysteine; mortality; pharmacogenetics
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Funding
- State Committee for Scientific Research [PBZ-KBN-090/P05/06/2003]
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Background The presence of metabolically important genetic polymorphisms may affect treatment efficacy in patients with malignancies. The objective of this prospective multicenter study Was to evaluate the role of selected polymorphisms of genes associated with metabolism of chemotherapeutic drugs as prognostic markers in children with acute lymphoblastic leukemia. Procedure. Genotyping for the presence of 7 genetic variants in 403 patients and analysis of death cases were performed. Results. Thirty-one children died before reaching remission maintenance phase. Genetic analysis revealed in this group increased frequency of homozygosity for c.677C>T polymorphism of the MTHFR gene (26% vs. 8% in the survivors; OR 4,09; 95% CI 1.67-10; adjusted for multiple testing P=0.028). Conclusion. Our data Suggest that modification of anti-leukemic treatment should be considered in patients homozygous for c.677C>T polymorphism. Pediatr Blood Cancer 2009;52:364-368 (C) 2008 Wiley-Liss, Inc.
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