Laboratory of Pharmacology, National Institute of Paediatrics, Mexico City, Mexico.
Epidemiological Surveillance Unit, National Institute of Respiratory Diseases, Mexico City, Mexico.
Biomarkers. 2020 Jun;25(4):331-340. doi: 10.1080/1354750X.2020.1754913. Epub 2020 Apr 30.
Ifosfamide (IFA) is an effective antineoplastic for solid tumours in children, although it is associated with high levels of systemic toxicity and causes death in some cases. The aim of this study was to determine whether the presence of certain allelic variants of genes , , and increases the risk of toxicity in children with solid tumours treated with ifosfamide. A total of 131 DNA samples were genotyped by real-time polymerase chain reaction (RT-PCR) using TaqMan probes. Toxicity was assessed using WHO criteria, and survival analysis was performed using Kaplan-Meier curves. The rs3745274 allelic variant in was associated with haematological toxicity, affecting neutrophils; variant rs2740574 was also associated with toxicity, affecting both leukocytes and neutrophils. Additionally, the gene variant rs776746 was found to affect haemoglobin. Our results show that allelic variants rs3745274 (, rs2740574 ( and rs776746 ( increase the risk for high haematological toxicity. 068/2013.
异环磷酰胺（IFO）是一种有效的儿童实体瘤抗肿瘤药物，尽管它与高水平的全身毒性有关，并在某些情况下导致死亡。本研究旨在确定是否存在某些基因的等位基因变体，如 、 、 ，会增加接受异环磷酰胺治疗的实体瘤儿童发生毒性的风险。总共对 131 个 DNA 样本进行了实时聚合酶链反应（RT-PCR），使用 TaqMan 探针进行基因分型。毒性评估采用世界卫生组织（WHO）标准，生存分析采用 Kaplan-Meier 曲线进行。 基因的 rs3745274 等位基因变体与血液学毒性有关，影响中性粒细胞；rs2740574 变体也与毒性有关，影响白细胞和中性粒细胞。此外，基因变体 rs776746 还影响血红蛋白。我们的研究结果表明，等位基因变体 rs3745274（ 、rs2740574（ 和 rs776746（ 增加了发生严重血液学毒性的风险。068/2013。
