1. Genome-Wide Association Study for Anthracycline-Induced Congestive Heart Failure
- Author
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Schneider, Bryan P, Shen, Fei, Gardner, Laura, Radovich, Milan, Li, Lang, Miller, Kathy D, Jiang, Guanglong, Lai, Dongbing, O'Neill, Anne, Sparano, Joseph A, Davidson, Nancy E, Cameron, David, Gradus-Pizlo, Irmina, Mastouri, Ronald A, Suter, Thomas M, Foroud, Tatiana, and Sledge, George W
- Subjects
Clinical Research ,Cancer ,Breast Cancer ,Clinical Trials and Supportive Activities ,Genetics ,Heart Disease ,Cardiovascular ,Patient Safety ,Prevention ,Human Genome ,Aging ,Anthracyclines ,Antibiotics ,Antineoplastic ,Breast Neoplasms ,Case-Control Studies ,Clinical Trials ,Phase III as Topic ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Heart Failure ,Humans ,Phenotype ,Polymorphism ,Single Nucleotide ,Prognosis ,Reproducibility of Results ,Risk Assessment ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeAnthracycline-induced congestive heart failure (CHF) is a rare but serious toxicity associated with this commonly employed anticancer therapy. The ability to predict which patients might be at increased risk prior to exposure would be valuable to optimally counsel risk-to-benefit ratio for each patient. Herein, we present a genome-wide approach for biomarker discovery with two validation cohorts to predict CHF from adult patients planning to receive anthracycline.Experimental designWe performed a genome-wide association study in 3,431 patients from the randomized phase III adjuvant breast cancer trial E5103 to identify single nucleotide polymorphism (SNP) genotypes associated with an increased risk of anthracycline-induced CHF. We further attempted candidate validation in two independent phase III adjuvant trials, E1199 and BEATRICE.ResultsWhen evaluating for cardiologist-adjudicated CHF, 11 SNPs had a P value
- Published
- 2017