ArticleNature genetics2015
A coding variant in RARG confers susceptibility to anthracycline-induced cardiotoxicity in childhood cancer.
Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 5 of them syntheses that pooled it.
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Who cites it
166 citing papers in PubMed, 5 syntheses or guidelines pooled it, 270 citations in OpenAlex.
- Influence of genetic biomarkers on cardiac diseases in childhood cancer survivors: a systematic review.The pharmacogenomics journal · 2025Pooled it
- Clinical and cost-effectiveness of pharmacogenomic testing for anthracycline-induced cardiotoxicity in childhood cancer: a systematic review and meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Pharmacogenetics of chemotherapy treatment response and -toxicities in patients with osteosarcoma: a systematic review.BMC cancer · 2022Pooled it
- Potential Gene Association Studies of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- Candidate Gene Association Studies of Anthracycline-induced Cardiotoxicity: A Systematic Review and Meta-analysis.Scientific reports · 2017Pooled it
- Pharmacogenomic Variability of Oral Baclofen Clearance and Clinical Response in Children With Cerebral Palsy.PM & R : the journal of injury, function, and rehabilitation · 2018Trial
- Childhood cancer and future cardiometabolic health.npj metabolic health and disease · 2026Review
- Genetic and Molecular Determinants of Cancer Therapy-Related Cardiovascular Toxicity.Cardiovascular toxicology · 2026Review
- CRISPR-cas systems in pharmacology: functional pharmacogenomics, drug screening, resistance, and therapeutic translation.Functional & integrative genomics · 2026Review
- Cardiovascular Risk Stratification and Surveillance in Cardio-Oncology: Mechanistic Foundations and Future Directions.Biomedicines · 2026Review
- Doxorubicin-Induced Cardiotoxicity in Breast Cancer: Mechanistic Pathways, Pharmacogenomic Modifiers, and Translational Strategies.Cardiovascular toxicology · 2026Review
- Physiologically relevant 3D CRISPR screening enhances mechanistic insight into chemical toxicity compared to 2D screening.Toxicology · 2026Article
- Cardiotoxicity of Antitumor Agents: Therapeutic Challenges in Heart Failure with Reduced and Preserved Ejection Fraction.International journal of molecular sciences · 2026Review
- Transcriptomic biomarkers related to cardiac disease in childhood cancer survivors: a case-control study.European heart journal · 2026Article
- Pharmacogenomic predictors of anthracycline-induced cardiotoxicity in breast cancer patients: a systematic review and meta-analysis.Cardio-oncology (London, England) · 2026Review
- CRISPR/Cas9 Screens Implicate RARA and SPNS1 in Doxorubicin Cardiotoxicity.JACC. CardioOncology · 2026Article
- Functional Genomics Illuminates Mechanisms of Anthracycline Cardiotoxicity.JACC. CardioOncology · 2026Article
- The role of pharmacogenetics in the therapy regimen of acute lymphoblastic leukemia in children: recent discoveries and future perspectives.Pharmacological reports : PR · 2026Review
- Caught in the crossfire: cardiac complications of cancer therapy.The Journal of clinical investigation · 2026Review
- predicTox: an integrated database of clinical risk frequencies and human gene expression signatures for cardiotoxic drugs.Database : the journal of biological databases and curation · 2026Article
106 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 18 institutions in 4 countries.
Funding
Abstract
Anthracyclines are used in over 50% of childhood cancer treatment protocols, but their clinical usefulness is limited by anthracycline-induced cardiotoxicity (ACT) manifesting as asymptomatic cardiac dysfunction and congestive heart failure in up to 57% and 16% of patients, respectively. Candidate gene studies have reported genetic associations with ACT, but these studies have in general lacked robust patient numbers, independent replication or functional validation. Thus, the individual variability in ACT susceptibility remains largely unexplained. We performed a genome-wide association study in 280 patients of European ancestry treated for childhood cancer, with independent replication in similarly treated cohorts of 96 European and 80 non-European patients. We identified a nonsynonymous variant (rs2229774, p.Ser427Leu) in RARG highly associated with ACT (P = 5.9 × 10(-8), odds ratio (95% confidence interval) = 4.7 (2.7-8.3)). This variant alters RARG function, leading to derepression of the key ACT genetic determinant Top2b, and provides new insight into the pathophysiology of this severe adverse drug reaction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.