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Predicting Anthracycline‐induced Cardiotoxicity in Children – Genome‐Wide Association Study
Author(s) -
Aminkeng Folefac,
Ross Colin JD,
Rassekh Rod S,
Brunham Liam R,
Weissman Cory,
Dube MariePierre,
Visscher Henk,
Rieder Michael J,
Carleton Bruce C,
Hayden Michael R
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.663.3
Subject(s) - pharmacogenomics , genome wide association study , medicine , cardiotoxicity , anthracycline , genotyping , cohort , oncology , pharmacogenetics , bioinformatics , genetics , biology , single nucleotide polymorphism , cancer , genotype , pharmacology , chemotherapy , gene , breast cancer
Identified genetic markers for anthracycline‐induced cardiotoxicity (ACT) explain only a small fraction of the variability of this phenotype, suggesting the presence of other, as‐of‐yet unidentified susceptibility loci. Therefore, our goal is to identify additional genetic markers with large effect size via genome‐wide association study (GWAS). Patients were recruited and clinically characterized (age at start of treatment, cumulative dose, gender, anthracycline and tumor type, radiation therapy involving the heart, follow‐up time and assessment of LV dysfunction) via the Canadian Pharmacogenomics Network for Drug Safety. We have recruited and clinically characterized over 400 patients from across Canada to serve as our discovery cohort and over 120 patients from the Emma Children's Hospital in Amsterdam, the Netherlands, to be used as our replication cohort. More patients are currently being recruited and the clinical characterization is ongoing. We are now genotyping samples with an Illumina GWAS panel and the statistical analyses will be underway soon using SVS/Helix Tree, SPSS, Epi Info, PLINK and R. Novel genetic predictors for ACT may become essential for screening patients before the start of treatment, comprehensive risk assessment and management, and evidence‐based treatment decisions, monitoring and prevention. This work was supported by CIHR, CFRI, and Genome BC.