
Evidence for association of SNPs in ABCB1 and CBR3, but not RAC2, NCF4, SLC28A3 or TOP2B, with chronic cardiotoxicity in a cohort of breast cancer patients treated with anthracyclines.
AIMS: Validation of associations for SNPs in RAC2, NCF4 and SLC28A3, identification of a novel association with a TOP2B SNP and screening 23 SNPs putatively relevant to anthracycline-induced cardiotoxicity. PATIENTS & METHODS: A total of 166 breast cancer patients treated with doxorubicin underwent echocardiogram, including 19 cases with systolic dysfunction (ejection fraction <55%) and 147 controls. Four high priority SNPs were tested in the primary analysis, with appropriate statistical correction, and 23 additional SNPs were screened in an uncorrected secondary analysis. RESULTS: Previously reported associations for RAC2, NCF4 and SLC28A3 could not be validated and a novel association with TOP2B was not discovered in this cohort (all p > 0.05), likely due to inadequate power. Two SNPs were identified in the uncorrected secondary analysis including a protective SNP in ABCB1 (3435C>T, p = 0.049) and a risk allele in CBR3 (V244M, p = 0.012). CONCLUSION: The associations reported in prior publications and those discovered in this secondary analysis require further replication in independent cohorts.
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Related Subject Headings
- rac GTP-Binding Proteins
- Polymorphism, Single Nucleotide
- Poly-ADP-Ribose Binding Proteins
- Pharmacology & Pharmacy
- NADPH Oxidases
- Membrane Transport Proteins
- Humans
- Genetic Predisposition to Disease
- Genetic Association Studies
- Female
Citation

Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- rac GTP-Binding Proteins
- Polymorphism, Single Nucleotide
- Poly-ADP-Ribose Binding Proteins
- Pharmacology & Pharmacy
- NADPH Oxidases
- Membrane Transport Proteins
- Humans
- Genetic Predisposition to Disease
- Genetic Association Studies
- Female