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The role of the MTHFR C677T polymorphism in methotrexate-induced toxicity in pediatric osteosarcoma patients

(2017) PHARMACOGENOMICS. 18(8). p.787-795
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Abstract
Osteosarcoma patients receive high doses of methotrexate (MTX). However, pharmacogenetic information remains limited and has mainly been investigated in leukemia so far. Patients & methods: We investigated the link between the MTHFR C677T genotype, toxicity levels (mucositis, MTX plasma level, hematological toxicity and hepatotoxicity) and survival of 48 pediatric osteosarcoma patients. Results: The TT genotype did not show more toxicity compared with the CC/CT genotype. However, plasma MTX levels were related with mucositis, but not with hematological toxicity, nor hepatotoxicity. Survival rates did not differ between homozygous and non-homozygous patients. Yet, homozygous patients had higher relapse risk. Conclusion: The MTHFR C667T polymorphism is not predictive for toxicity or overall survival, but could be used for relapse risk stratification.
Keywords
methotrexate, MTHFR, osteosarcoma, outcome, pediatric, toxicity, ACUTE LYMPHOBLASTIC-LEUKEMIA, METHYLENETETRAHYDROFOLATE REDUCTASE C677T, CHRONIC MYELOGENOUS LEUKEMIA, HIGH-GRADE OSTEOSARCOMA, HIGH-DOSE METHOTREXATE, CELL TRANSPLANTATION, GENE POLYMORPHISM, LIVER TOXICITY, SURVIVAL, THERAPY

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Chicago
Lambrecht, Loes, Charlotte Sleurs, Veerle Labarque, Catharina Dhooge, Annouschka Laenen, Friedl Sinnaeve, Marleen Renard, and Anne Uyttebroeck. 2017. “The Role of the MTHFR C677T Polymorphism in Methotrexate-induced Toxicity in Pediatric Osteosarcoma Patients.” Pharmacogenomics 18 (8): 787–795.
APA
Lambrecht, L., Sleurs, C., Labarque, V., Dhooge, C., Laenen, A., Sinnaeve, F., Renard, M., et al. (2017). The role of the MTHFR C677T polymorphism in methotrexate-induced toxicity in pediatric osteosarcoma patients. PHARMACOGENOMICS, 18(8), 787–795.
Vancouver
1.
Lambrecht L, Sleurs C, Labarque V, Dhooge C, Laenen A, Sinnaeve F, et al. The role of the MTHFR C677T polymorphism in methotrexate-induced toxicity in pediatric osteosarcoma patients. PHARMACOGENOMICS. 2017;18(8):787–95.
MLA
Lambrecht, Loes et al. “The Role of the MTHFR C677T Polymorphism in Methotrexate-induced Toxicity in Pediatric Osteosarcoma Patients.” PHARMACOGENOMICS 18.8 (2017): 787–795. Print.
@article{8522919,
  abstract     = {Osteosarcoma patients receive high doses of methotrexate (MTX). However, pharmacogenetic information remains limited and has mainly been investigated in leukemia so far. Patients & methods: We investigated the link between the MTHFR C677T genotype, toxicity levels (mucositis, MTX plasma level, hematological toxicity and hepatotoxicity) and survival of 48 pediatric osteosarcoma patients. Results: The TT genotype did not show more toxicity compared with the CC/CT genotype. However, plasma MTX levels were related with mucositis, but not with hematological toxicity, nor hepatotoxicity. Survival rates did not differ between homozygous and non-homozygous patients. Yet, homozygous patients had higher relapse risk. Conclusion: The MTHFR C667T polymorphism is not predictive for toxicity or overall survival, but could be used for relapse risk stratification.},
  author       = {Lambrecht, Loes and Sleurs, Charlotte and Labarque, Veerle and Dhooge, Catharina and Laenen, Annouschka and Sinnaeve, Friedl and Renard, Marleen and Uyttebroeck, Anne},
  issn         = {1462-2416},
  journal      = {PHARMACOGENOMICS},
  keywords     = {methotrexate,MTHFR,osteosarcoma,outcome,pediatric,toxicity,ACUTE LYMPHOBLASTIC-LEUKEMIA,METHYLENETETRAHYDROFOLATE REDUCTASE C677T,CHRONIC MYELOGENOUS LEUKEMIA,HIGH-GRADE OSTEOSARCOMA,HIGH-DOSE METHOTREXATE,CELL TRANSPLANTATION,GENE POLYMORPHISM,LIVER TOXICITY,SURVIVAL,THERAPY},
  language     = {eng},
  number       = {8},
  pages        = {787--795},
  title        = {The role of the MTHFR C677T polymorphism in methotrexate-induced toxicity in pediatric osteosarcoma patients},
  url          = {http://dx.doi.org/10.2217/pgs-2017-0013},
  volume       = {18},
  year         = {2017},
}

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