Context: 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. Objective: The aim of this study was to determine whether the presence of certain allelic variants of genes CYP2B6, CYP2C9, CYP3A4 and CYP3A5 increases the risk of toxicity in children with solid tumours treated with ifosfamide.Materials and methods: 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.Results: The rs3745274 allelic variant in CYP2B6 was associated with haematological toxicity, affecting neutrophils; CYP3A4 variant rs2740574 was also associated with toxicity, affecting both leukocytes and neutrophils. Additionally, the CYP3A5 gene variant rs776746 was found to affect haemoglobin.Conclusions: Our results show that allelic variants rs3745274 (CYP2B6), rs2740574 (CYP34) and rs776746 (CYP3A5) increase the risk for high haematological toxicity.Clinical trial registration: 068/2013.

中文翻译：

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CYP450基因等位基因变体的分析可以预测异环磷酰胺对墨西哥小儿患者的毒性。

背景：异环磷酰胺（IFA）是儿童实体瘤的有效抗肿瘤药，尽管它与高水平的全身毒性相关并在某些情况下会导致死亡。目的：本研究的目的是确定CYP2B6，CYP2C9，CYP3A4和CYP3A5基因的某些等位基因变体的存在是否会增加异环磷酰胺治疗的实体瘤患儿的中毒风险。材料和方法：总共131个DNA样品使用TaqMan探针通过实时聚合酶链反应（RT-PCR）对它们进行基因分型。结果：CYP2B6基因的rs3745274等位基因变异与血液学毒性有关，影响中性粒细胞。CYP3A4变体rs2740574也与毒性相关，影响白细胞和中性粒细胞。此外，发现CYP3A5基因变体rs776746影响血红蛋白。结论：我们的研究结果表明，等位基因变体rs3745274（CYP2B6），rs2740574（CYP34）和rs776746（CYP3A5）增加了发生高血液毒性的风险。临床试验注册：068/2013 。