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

Overview

Journal J Cardiovasc Dev Dis

Specialty Cardiology & Vascular Diseases

Date 2023 Jun 27

PMID 37367397

Authors

Gintare Muckiene

Domas Vaitiekus

Diana Zaliaduonyte

Agne Bartnykaite

Jurgita Plisiene

Vytautas Zabiela

Elona Juozaityte

Renaldas Jurkevicius

Affiliations

Soon will be listed here.

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.

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