Daniel L Hertz1, Megan V Caram2, Kelley M Kidwell3, Jacklyn N Thibert2, Christina Gersch2, Nicholas J Seewald3, Jeffrey Smerage2, Melvyn Rubenfire4, N Lynn Henry2, Kathleen A Cooney2,5, Monika Leja4, Jennifer J Griggs2, James M Rae2,6. 1. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA. 2. Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. 3. Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA. 4. Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. 5. Department of Urology, University of Michigan Health System, Ann Arbor, MI 48109, USA. 6. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Abstract
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.
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 cancerpatients 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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