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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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Organization
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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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.
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.
Chicago author-date
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.
Chicago author-date (all authors)
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.
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.
IEEE
[1]
L. Lambrecht et al., “The role of the MTHFR C677T polymorphism in methotrexate-induced toxicity in pediatric osteosarcoma patients,” PHARMACOGENOMICS, vol. 18, no. 8, pp. 787–795, 2017.
@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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