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Genetic Susceptibility to Anthracycline-Induced Cardiotoxicity in Australian Pediatric Cancer Patients

Year: 2026

Type: article

Abstract: urvival rates for childhood cancers have improved over the past decades, due in part to the use of anthracyclines, which are highly effective chemotherapy agents and used in more than half of pediatric chemotherapy regimens.Despite their antitumor efficacy, their use is limited by the risk of anthracycline-induced cardiotoxicity (ACT), which commonly presents as symptomatic cardiomyopathy or asymptomatic left ventricular dysfunction.Risk is influenced by cumulative exposure and clinical factors, yet these do not fully explain interindividual susceptibility.Germ line variants in genes related to drug transport, metabolism, oxidative stress, myocardial structure, DNA damage response, and intracellular signaling have been associated with ACT, although replication has been inconsistent.1 This study investigated genetic susceptibility to ACT in Australian pediatric cancer survivors by assessing previously ACT-associated variants and conducting an exploratory analysis.Ethics approval was obtained from the Royal Children's Hospital HREC (HREC38130), with written consent from participants selected from 2 pediatric cohorts (ACTive, ACOR).Eligible patients had a cancer diagnosis, anthracycline exposure, baseline echocardiography, no pre-existing cardiac abnormality, and a sample available in the biobank.ACT cases were identified using Cancer Therapy-Related Cardiac What is the clinical question being addressed?Which germ line variants are associated with anthracycline-induced cardiotoxicity in Australian pediatric cancer survivors?What is the main finding?TTN rs2303838 showed a nominally protective association, whereas SLC28A3 rs7853758 was associated with increased risk; exploratory analyses highlighted 5 novel candidate genes with potential relevance to cardiotoxicity.

Source: JACC Advances

DOI: 10.1016/j.jacadv.2026.103105