CYP450 Gene Polymorphisms and the Risk of Taxane-Induced Neurotoxicity in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

IF 2 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biomarkers Pub Date : 2025-06-25 DOI:10.1080/1354750X.2025.2522892

Nayara Moretti Rozalem, Bárbara de Moura Moreira, Isabella Pimentel Braz, Isabella Caroline de Oliveira Barretto, Ana Laura Ayumi Zanoni Chiba, Angélica Augusta Grigoli Dominato, Francisco Cezar Aquino de Moraes

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引用次数: 0

Abstract

Background: Breast cancer (BC) is the most common cancer in women. Taxanes are widely used, but their neurotoxicity affects patients' quality of life. Genetic polymorphisms in CYP450 enzymes influence taxane metabolism, leading to variability in toxicity risk.

Methods: A literature search was conducted to identify studies on the association between CYP450 polymorphisms and Taxane-Induced Peripheral Neuropathy (TIPN) in BC patients. Odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using a random-effects model in RStudio.

Results: Nine studies with 3034 patients were included. Overall CYP polymorphisms showed a significant association with TIPN (OR: 1.2877, 95% CI: 1.0262-1.6157). CYP1B1 polymorphism had an inconsistent link to TIPN by OR of 1.1524 (95% CI: 0.7441-1.7849). CYP2C8 polymorphism demonstrated the strongest association (OR: 1.5532, 95% CI: 1.2013-2.0082; HR: 1.5236, 95% CI: 1.1317-2.0512). CYP3A4 showed no significant association (OR: 1.0988, 95% CI: 0.5022-2.4404).

Conclusions: CYP2C8 polymorphisms were significantly linked to TIPN. While CYP1B1 showed inconsistent results, CYP3A4 had no significant association. These findings imply that CYP2C8 genetic variations may affect taxane metabolism and neurotoxicity risk, indicating that pharmacogenomic profiling could help personalize chemotherapy and reduce adverse effects.

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CYP450基因多态性与紫杉烷诱导乳腺癌患者神经毒性的风险：一项系统综述和荟萃分析。

背景：乳腺癌（BC）是女性中最常见的癌症。紫杉烷被广泛使用，但其神经毒性影响患者的生活质量。CYP450酶的遗传多态性影响紫杉烷代谢，导致毒性风险的变异。方法：通过文献检索，确定CYP450多态性与BC患者紫杉烷诱导的周围神经病变（TIPN）之间的关系。使用RStudio中的随机效应模型估计95%置信区间（CI）的优势比（OR）和风险比（HR）。结果：纳入9项研究，共3034例患者。总体CYP多态性与TIPN显著相关（OR: 1.2877, 95% CI: 1.0262-1.6157）。CYP1B1多态性与TIPN的关联不一致，OR为1.1524 （95% CI: 0.7441-1.7849）。CYP2C8多态性表现出最强的相关性(OR: 1.5532, 95% CI: 1.2013-2.0082；Hr: 1.5236, 95% ci: 1.1317-2.0512)。CYP3A4无显著相关性（OR: 1.0988, 95% CI: 0.5022-2.4404）。结论：CYP2C8多态性与TIPN显著相关。而CYP1B1显示不一致的结果，CYP3A4无显著相关性。这些发现表明CYP2C8基因变异可能影响紫杉烷代谢和神经毒性风险，表明药物基因组学分析可以帮助个性化化疗并减少不良反应。

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

Biomarkers 医学-毒理学

CiteScore

5.00

自引率

3.80%

发文量

140

审稿时长

3 months

期刊介绍： The journal Biomarkers brings together all aspects of the rapidly growing field of biomarker research, encompassing their various uses and applications in one essential source. Biomarkers provides a vital forum for the exchange of ideas and concepts in all areas of biomarker research. High quality papers in four main areas are accepted and manuscripts describing novel biomarkers and their subsequent validation are especially encouraged: • Biomarkers of disease • Biomarkers of exposure • Biomarkers of response • Biomarkers of susceptibility Manuscripts can describe biomarkers measured in humans or other animals in vivo or in vitro. Biomarkers will consider publishing negative data from studies of biomarkers of susceptibility in human populations.