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.


Journal Article

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.

Full Text

Cited Authors

  • Hertz, DL; Caram, MV; Kidwell, KM; Thibert, JN; Gersch, C; Seewald, NJ; Smerage, J; Rubenfire, M; Henry, NL; Cooney, KA; Leja, M; Griggs, JJ; Rae, JM

Published Date

  • February 2016

Published In

Volume / Issue

  • 17 / 3

Start / End Page

  • 231 - 240

PubMed ID

  • 26799497

Pubmed Central ID

  • 26799497

Electronic International Standard Serial Number (EISSN)

  • 1744-8042

Digital Object Identifier (DOI)

  • 10.2217/pgs.15.162


  • eng

Conference Location

  • England