Genetic polymorphisms of ABCC2 and CBR3 can influence the efficacy and toxicity of doxorubicin therapy in Egyptian patients with non-Hodgkin lymphoma.

IF 1.2 4区医学 Q4 PHARMACOLOGY & PHARMACY

Xenobiotica Pub Date : 2025-05-01 Epub Date: 2025-05-29 DOI:10.1080/00498254.2025.2508814

Hagar A Elmekawy, Khaled Abdelkawy, Galal Magdy, Emad Sadaka, Gamal El-Azab, Ahmed Ali, Noha El-Khodary, Fawzy Elbarbry

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Abstract

This study investigated the impact of single nucleotide polymorphisms (SNPs) in genes involved in doxorubicin (DOX) transport and metabolism on clinical outcomes and toxicity in Egyptian patients with non-Hodgkin lymphoma.

Ninety-two patients received at least six DOX treatment cycles. SNP genotyping was performed using real-time PCR with high-resolution melting analysis. Laboratory tests were conducted at baseline, during, and after treatment.

The AA genotype of ABCC2 (rs8187710) showed the strongest association with elevated DOX plasma levels and a significantly increased risk of acute cardiotoxicity (OR 26.9; 95% CI: 1.47-492; p = 0.026). The GA genotype was linked to a lower complete response rate and increased risks of leukopoenia (OR 2.66; 95% CI: 1.07-6.61; p = 0.034) and lymphocytopenia (OR 10; 95% CI: 3.57-27.9; p < 0.0001), with intermediate peak DOX levels. For CBR3 (rs8133052), the GA genotype was significantly associated with a higher risk of anaemia (OR 3.5; 95% CI: 1.05-11.7; p = 0.042), acute cardiotoxicity (OR 4.4; 95% CI: 1.86-11.5; p = 0.002), cardiac-related symptoms, and higher peak plasma DOX levels, along with reduced complete response.

Polymorphisms in ABCC2 and CBR3 genes may contribute to individual variability in DOX-related toxicity and treatment response.

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ABCC2和CBR3基因多态性可影响阿霉素治疗埃及非霍奇金淋巴瘤患者的疗效和毒性。

目的：本研究探讨了多柔比星（DOX）转运和代谢相关基因的单核苷酸多态性（snp）对埃及非霍奇金淋巴瘤患者临床结局和毒性的影响。方法：92例患者接受至少6个DOX治疗周期。采用实时PCR高分辨率熔融分析进行SNP基因分型。在基线、治疗期间和治疗后进行实验室检查。结果：ABCC2 （rs8187710）的AA基因型与血浆DOX水平升高和急性心脏毒性风险显著增加(OR 26.9；95% ci: 1.47-492；p = 0.026)。GA基因型与较低的完全缓解率和白细胞减少的风险增加有关(OR 2.66；95% ci: 1.07-6.61；p = 0.034)和淋巴细胞减少症(OR 10；95% ci: 3.57-27.9；p p = 0.042)，急性心脏毒性(OR 4.4；95% ci: 1.86-11.5；p = 0.002)，心脏相关症状，血浆DOX峰值升高，同时完全缓解降低。结论：ABCC2和CBR3基因多态性可能与dox相关毒性和治疗反应的个体差异有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Xenobiotica 医学-毒理学

CiteScore

3.80

自引率

5.60%

发文量

审稿时长

2 months

期刊介绍： Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology