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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.

Publication ,  Journal Article
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 in: Pharmacogenomics
February 2016

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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Published In

Pharmacogenomics

DOI

EISSN

1744-8042

Publication Date

February 2016

Volume

17

Issue

3

Start / End Page

231 / 240

Location

England

Related Subject Headings

  • rac GTP-Binding Proteins
  • RAC2 GTP-Binding Protein
  • Polymorphism, Single Nucleotide
  • Poly-ADP-Ribose Binding Proteins
  • Pharmacology & Pharmacy
  • NADPH Oxidases
  • Membrane Transport Proteins
  • Humans
  • Genetic Predisposition to Disease
  • Genetic Association Studies
 

Citation

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Hertz, D. L., Caram, M. V., Kidwell, K. M., Thibert, J. N., Gersch, C., Seewald, N. J., … Rae, J. M. (2016). 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. Pharmacogenomics, 17(3), 231–240. https://doi.org/10.2217/pgs.15.162
Hertz, Daniel L., Megan V. Caram, Kelley M. Kidwell, Jacklyn N. Thibert, Christina Gersch, Nicholas J. Seewald, Jeffrey Smerage, et al. “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.Pharmacogenomics 17, no. 3 (February 2016): 231–40. https://doi.org/10.2217/pgs.15.162.
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. 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. Pharmacogenomics. 2016 Feb;17(3):231–240.
Journal cover image

Published In

Pharmacogenomics

DOI

EISSN

1744-8042

Publication Date

February 2016

Volume

17

Issue

3

Start / End Page

231 / 240

Location

England

Related Subject Headings

  • rac GTP-Binding Proteins
  • RAC2 GTP-Binding Protein
  • Polymorphism, Single Nucleotide
  • Poly-ADP-Ribose Binding Proteins
  • Pharmacology & Pharmacy
  • NADPH Oxidases
  • Membrane Transport Proteins
  • Humans
  • Genetic Predisposition to Disease
  • Genetic Association Studies