The influence of MTHFR C677T polymorphism on methotrexate toxicity in pediatric acute lymphoblastic leukemia
Published 2017-07-01
Keywords
- acute lymphoblastic leukemia,
- methotrexate,
- toxic effects,
- MTHFR,
- polymorphisms
How to Cite
Abstract
In current protocols for treatment of acute lymphoblastic leukemia in childhood methotrexate (MTX) is one of the crucial cytostatics. The occurrence of MTX toxicity is still а great problem because of the interpatient differences in drug metabolism. These differences may be due to polymorphisms of genes involved in the folate metabolism. The present study was carried out to determine the prevalence of MTHFR C677T polymorphism in children with acute lymphoblastic leukemia (ALL). Also the effect of the genotype on the toxic effects during therapy with high doses of МТХ in 45 patients with ALL treated in accordance with the protocol ALL BFM 95 and ALL BFM 2000 was evaluated. All 45 patients with ALL were genotyped for MTHFR C677T polymorphism. Correlation with the presence of a certain polymorphism and toxic effects of the chemotherapy with high doses of МТХ was made in the Department for hematology and oncology at the University Clinic for children's diseases – Skopje. The control group included 32 healthy patients. In the study group 24 (53.3%) children had a wild type of polymorphism (CC), 15 (33.33%) children were heterozygous (CT) for MTHFR C677T polymorphism, and 6 (13.33%) children were homozygous for the variant type of the polymorphism (ТТ). The correlation of the genotype with МТХ toxicity indicated a statistical significance only for oral mucositis, while for the other toxic effects there was no statistically significant correlation. In our study the results indicated that oral mucositis was statistically significantly more frequently identified in the case of the variant carriers for this polymorphism. For the other toxic effects caused by the therapy with high doses of МТХ no statistically significant correlation with MTHFR C677T polymorphism was identified. This occurrence maybe due to the small number of patients analyzed in this study and the possible protective influence of other genetic polymorphisms included in the folate metabolism, which were not subject to consideration of this study.
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