ArticlePharmacogenetics and genomics2017
Genome-wide association study of cardiotoxicity in the NCCTG N9831 (Alliance) adjuvant trastuzumab trial.
Article in Pharmacogenetics and genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 3 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Meta-analysis of genome-wide association studies for cancer therapy-related cardiovascular dysfunction and functional mapping highlight an intergenic region close to TP63.Scientific reports · 2024Pooled it
- Pharmacogenetics of chemotherapy treatment response and -toxicities in patients with osteosarcoma: a systematic review.BMC cancer · 2022Pooled it
- Genetic and RNA-related molecular markers of trastuzumab-chemotherapy-associated cardiotoxicity in HER2 positive breast cancer: a systematic review.BMC cancer · 2022Pooled it
- Meta-Analysis of Genome-Wide Association Studies of Doxorubicin-Induced Arrhythmia IdentifiesCirculation. Genomic and precision medicine · 2026Article
- Doxorubicin-Induced Cardiotoxicity in Breast Cancer: Mechanistic Pathways, Pharmacogenomic Modifiers, and Translational Strategies.Cardiovascular toxicology · 2026Review
- Gain-of-Function VariantCirculation. Genomic and precision medicine · 2026Article
- Meta-analysis of genome-wide association studies of doxorubicin-induced arrhythmia identifiesmedRxiv : the preprint server for health sciences · 2025Article
- Anthracyclines induce global changes in cardiomyocyte chromatin accessibility that overlap with cardiovascular disease loci.PLoS genetics · 2025Article
- Drugs Metabolism-Related Genes Variants Impact on Anthracycline-Based Chemotherapy Induced Subclinical Cardiotoxicity in Breast Cancer Patients.International journal of molecular sciences · 2025Article
- SNP's use as a potential chemotoxicity stratification tool in breast cancer: from bench to clinic.Functional & integrative genomics · 2025Review
- Genetic Background in Patients with Cancer Therapy-Induced Cardiomyopathy.Journal of clinical medicine · 2025Review
- Genetic factors in the pathogenesis of cardio-oncology.Journal of translational medicine · 2024Review
- Harnessing iPSCs to Dissect Causality in Anthracycline-Induced Cardiotoxicity: All That Fits Are Not Hits.JACC. CardioOncology · 2024Article
- Racial Disparity in Anthracycline-induced Cardiotoxicity in Breast Cancer Patients.Biomedicines · 2023Review
- Review
- Replication of genetic associations of chemotherapy-related cardiotoxicity in the adjuvant NSABP B-31 clinical trial.Frontiers in oncology · 2023Article
- TRPC6 N338S is a gain-of-function mutant identified in patient with doxorubicin-induced cardiotoxicity.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Exploration of the amino acid metabolic signature in anthracycline-induced cardiotoxicity using an optimized targeted metabolomics approach based on UPLC-MS/MS.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Novel molecular biomarkers of cancer therapy-induced cardiotoxicity in adult population: a scoping review.ESC heart failure · 2022Article
- Genetics of cancer therapy-associated cardiotoxicity.Journal of molecular and cellular cardiology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesThe major clinical side effect of the ERBB2-targeted breast cancer therapy, trastuzumab, is a decline in the left ventricular ejection fraction (LVEF). Improved markers are needed to better identify patients susceptible to cardiotoxicity.
methodsThe NCCTG N9831 trial compared adjuvant doxorubicin and cyclophosphamide followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or concurrent paclitaxel and trastuzumab (arm C) in patients with HER2-positive breast cancer. A genome-wide association study was performed on all patients with available DNA (N=1446). We used linear regression to identify single nucleotide polymorphisms (SNPs) associated with decline in LVEF, adjusting for age, baseline LVEF, antihypertensive medications, and the first two principle components.
resultsIn total, 618 863 SNPs passed quality control and DNA from 1191 patients passed genotyping quality control and were identified as Whites of non-Hispanic origin. SNPs at six loci were associated with a decline in LVEF (P=7.73×10 to 8.93×10), LDB2, BRINP1, chr6 intergenic, RAB22A, TRPC6, and LINC01060, in patients who received chemotherapy plus trastuzumab (arms BC, N=800). None of these loci were significant in patients who received chemotherapy only (arm A, N=391) and did not increase in significance in the combined analysis of all patients. We did not observe association, P<0.05, with SNPs previously associated with trastuzumab-induced cardiotoxicity at ERBB2, I655V, and P1170A. We replicated association, P<0.05, with SNPs previously associated with anthracycline-induced cardiotoxicity at CBR3 and ABCB1.
conclusionOur study identified six putative novel cardiotoxicity loci in patients treated with combination chemotherapy and trastuzumab that require further investigation and confirmed known associations of anthracycline-induced cardiotoxicity.
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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.