Lambrecht Loes, Sleurs Charlotte, Labarque Veerle, Dhooge Catharina, Laenen Annouschka, Sinnaeve Friedl, Renard Marleen, Uyttebroeck Anne
Department of Pediatrics, University Hospital Leuven, Leuven, Belgium.
Department of Reproduction & Regeneration, Catholic University Leuven, Leuven, Belgium.
Pharmacogenomics. 2017 Jun;18(8):787-795. doi: 10.2217/pgs-2017-0013. Epub 2017 Jun 8.
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.
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.
The MTHFR C667T polymorphism is not predictive for toxicity or overall survival, but could be used for relapse risk stratification.
骨肉瘤患者接受高剂量甲氨蝶呤（MTX）治疗。然而，药物遗传学信息仍然有限，迄今为止主要在白血病中进行了研究。
我们调查了48例儿童骨肉瘤患者的亚甲基四氢叶酸还原酶（MTHFR）C677T基因型、毒性水平（粘膜炎、MTX血药浓度、血液学毒性和肝毒性）与生存之间的联系。
与CC/CT基因型相比，TT基因型并未表现出更高的毒性。然而，MTX血药浓度与粘膜炎相关，但与血液学毒性和肝毒性无关。纯合子患者和非纯合子患者的生存率没有差异。然而，纯合子患者的复发风险更高。
MTHFR C667T多态性不能预测毒性或总生存期，但可用于复发风险分层。
