Authors
Marie-A Chaix, Neha Parmar, Caroline Kinnear, Myriam Lafreniere-Roula, Oyediran Akinrinade, Roderick Yao, Anastasia Miron, Emily Lam, Guoliang Meng, Anne Christie, Ashok Kumar Manickaraj, Stacey Marjerrison, Rejane Dillenburg, Mylène Bassal, Jane Lougheed, Shayna Zelcer, Herschel Rosenberg, David Hodgson, Leonard Sender, Paul Kantor, Cedric Manlhiot, James Ellis, Luc Mertens, Paul C Nathan, Seema Mital
Publication date
2020/12/1
Journal
Cardio Oncology
Volume
2
Issue
5
Pages
690-706
Publisher
American College of Cardiology Foundation
Description
Background
Despite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging.
Objectives
This study sought to develop a clinical and genetic risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors.
Methods
We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (≤250 mg/m2), and 106 control patients with preserved left ventricular ejection fraction despite doxorubicin >250 mg/m2 were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between case patients and control patients. The expression levels of 5 top-ranked genes were evaluated in human induced pluripotent stem cell–derived …
Total citations
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