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. (February 2016)

• Record Type: Journal Article
• Authors: Hertz, Daniel L; Caram, Megan V; Kidwell, Kelley M; Thibert, Jacklyn N; Gersch, Christina; Seewald, Nicholas J; Smerage, Jeffrey; Rubenfire, Melvyn; Henry, N Lynn; Cooney, Kathleen A; Leja, Monika; Griggs, Jennifer J; Rae, James M
• Is Part Of: Pharmacogenomics. Volume 17:Number 3(2016)
• Page Start: 231
• Page End: 240
• Publication Date: 2016-02
• Subjects: ABCB1 -- anthracycline -- cardiotoxicity -- CBR3 -- doxorubicin -- NCF4 -- pharmacogenetic -- RAC2 -- SLC28A3 -- systolic dysfunction -- TOP2B; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.15.162
• Languages: English
• ISSNs: 1462-2416

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.