Evidence for Association of SNPs in <i>ABCB1</i> and <i>CBR3</i> , but not <i>RAC2, NCF4, SLC28A3</i> or <i>TOP2B</i> , with Chronic Cardiotoxicity in a Cohort of Breast Cancer Patients Treated with Anthracyclines

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.