Dataset Information

Genetic polymorphism of CYP3A4 is associated with poor response to ifosfamide treatment in children with solid embryonic tumors.

ABSTRACT:

Introduction

The CYP450 complex participates in the metabolism of ifosfamide, an antineoplastic drug used to treat solid tumors. CYP450 genes contain several single nucleotide polymorphisms (SNPs) that confer different activity towards the enzyme. The aim of our study was to analyze gene frequencies of allelic variants and their association with ifosfamide blood levels and patient prognosis.

Material and methods

148 DNA samples from children were analyzed. Genotyping was performed by real-time PCR with TaqMan probes and ifosfamide levels were determined in dried blood drop by UPLCMS/MS.

Results

Ifosfamide levels increased according to the genotype, and patients with the variant rs1799853 in CYP2C9 genotype CC had lower levels of ifosfamide (median = 1.8 μmol/l, Q₂₅ 0.9-Q₇₅ 4.6) compared with patients with genotype TT + CT (median = 2.8 μmol/l, Q₂₅ 1.9-Q₇₅ 5.1), p < 0.001. In the case of the rs2740574 variant in the CYP3A4 gene, patients with normal genotype (TT) presented median = 1.4 μmol/l, (Q₂₅ 0.7-Q₇₅ 2.7), while patients with the CC + TC genotype had higher levels of ifosfamide (median = 2.0 μmol/l, Q₂₅ 1.0-Q₇₅ 4.3), p = 0.024. In addition, patients with CC + CT genotype of this variant had a higher risk of non-response to treatment compared to patients with TT genotype (RR = 1.3, 95% CI: 1.07-1.59, p = 0.03).

Conclusions

Polymorphisms in CYP2C9 and CYP3A4 genes are associated with high levels of ifosfamide. In addition, the polymorphism rs2740574 in CYP3A4 was associated with a worse therapeutic response.

SUBMITTER: Espindola LMT

PROVIDER: S-EPMC8641500 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Genetic polymorphism of <i>CYP3A4</i> is associated with poor response to ifosfamide treatment in children with solid embryonic tumors.

Espindola Luz María Torres LMT López Manuel De JesÚs Castillejos MJC Flores Armando De Uña AU Espinosa Liliana Rivera LR Granados Julio J Pacheco Juan Luis Chávez JLC García Martín Pérez MP Cervantes Ma Teresa Ramos MTR Méndez Vilma Carolina Bekker VCB Doño Susana Hernández SH Ruíz Gómez Daniela D

Archives of medical science : AMS 20190717 6

<h4>Introduction</h4>The CYP450 complex participates in the metabolism of ifosfamide, an antineoplastic drug used to treat solid tumors. <i>CYP450</i> genes contain several single nucleotide polymorphisms (SNPs) that confer different activity towards the enzyme. The aim of our study was to analyze gene frequencies of allelic variants and their association with ifosfamide blood levels and patient prognosis.<h4>Material and methods</h4>148 DNA samples from children were analyzed. Genotyping was pe ...[more]

PMID: 34900058

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