ATP结合盒转运蛋白基因多态性对乳腺癌患者蒽环类药物诱导的早期心脏毒性的影响

The Impact of Polymorphisms in ATP-Binding Cassette Transporter Genes on Anthracycline-Induced Early Cardiotoxicity in Patients with Breast Cancer.

作者信息

Muckiene Gintare, Vaitiekus Domas, Zaliaduonyte Diana, Bartnykaite Agne, Plisiene Jurgita, Zabiela Vytautas, Juozaityte Elona, Jurkevicius Renaldas

机构信息

Cardiology Clinic, Medical Academy, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.

Department of Cardiology, Hospital of Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania.

出版信息

J Cardiovasc Dev Dis. 2023 May 26;10(6):232. doi: 10.3390/jcdd10060232.

DOI:10.3390/jcdd10060232

PMID:37367397

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10299506/

Abstract

BACKGROUND

Cardiac side effects associated with anthracycline-based treatment may seriously compromise the prognosis of patients with breast cancer (BC). Evidence shows that genes that operate in drug metabolism can influence the risk of anthracycline-induced cardiotoxicity (AIC). ATP-binding cassette (ABC) transporters could serve as one of the potential biomarkers for AIC risk stratification. We aimed to determine the link between single-nucleotide polymorphisms (SNPs) in several genes ( rs1045642, rs4148350, rs3743527) and cardiotoxicity.

METHODS

The study included 71 patients with BC, who were treated with doxorubicin-based chemotherapy. Two-dimensional echocardiography and speckle-tracking echocardiography were performed. AIC was defined as a new decrease of 10 percentage points in the left ventricular ejection fraction (LVEF). SNPs in and genes were evaluated using real-time PCR.

RESULTS

After a cumulative dose of 236.70 mg/m of doxorubicin, 28.2% patients met the criteria of AIC. Patients who developed AIC had a larger impairment in left ventricular systolic function compared to those who did not develop AIC (LVEF: 50.20 ± 2.38% vs. 55.41 ± 1.13%, < 0.001; global longitudinal strain: -17.03 ± 0.52% vs. -18.40 ± 0.88%, < 0.001). The rs4148350 TG genotype was associated with higher rates of cardiotoxicity (TG vs. GG OR = 8.000, 95% CI = 1.405-45.547, = 0.019).

CONCLUSIONS

The study showed that rs4148350 is associated with AIC and could be a potential biomarker to assess the risk of treatment side effects in patients with BC.

摘要

背景

基于蒽环类药物的治疗相关的心脏副作用可能会严重影响乳腺癌（BC）患者的预后。有证据表明，参与药物代谢的基因可影响蒽环类药物诱导的心脏毒性（AIC）风险。ATP结合盒（ABC）转运蛋白可作为AIC风险分层的潜在生物标志物之一。我们旨在确定几个基因（rs1045642、rs4148350、rs3743527）中的单核苷酸多态性（SNP）与心脏毒性之间的联系。

方法

该研究纳入了71例接受基于多柔比星化疗的BC患者。进行了二维超声心动图和斑点追踪超声心动图检查。AIC定义为左心室射血分数（LVEF）新下降10个百分点。使用实时PCR评估和基因中的SNP。

结果

在累积剂量为236.70mg/m的多柔比星后，28.2%的患者符合AIC标准。发生AIC的患者与未发生AIC的患者相比，左心室收缩功能受损更大（LVEF：50.20±2.38%对55.41±1.13%，<0.001；整体纵向应变：-17.03±0.52%对-18.40±0.88%，<0.001）。rs4148350 TG基因型与更高的心脏毒性发生率相关（TG对GG OR = 8.000，95%CI = 1.405 - 45.547，= 0.019）。