Polymorphisms of ABCC5 and NOS3 genes influence doxorubicin cardiotoxicity in survivors of childhood acute lymphoblastic leukemia

M. Krajinovic, J. Elbared, S. Drouin, L. Bertout, A. Rezgui, M. Ansari, M. J. Raboisson, Steven E Lipshultz, L. B. Silverman, S. E. Sallan, D. S. Neuberg, J. L. Kutok, C. Laverdière, D. Sinnett, G. Andelfinger

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27 Scopus citations

Abstract

Anthracyclines are efficient chemotherapy agents. However, their use is limited by anthracycline-induced cardiotoxicity (CT). We investigated the influence of polymorphisms in doxorubicin metabolic and functional pathways on late-onset CT as estimated by echocardiography in 251 childhood acute lymphoblastic leukemia (cALL) patients. Association analyses revealed a modulating effect of two variants: A-1629 T in ABCC5, an ATP-binding cassette transporter, and G894T in the NOS3 endothelial nitric oxide synthase gene. Individuals with the ABCC5 TT-1629 genotype had an average of 8–12% reduction of ejection (EF) and shortening fractions (SF; EF: P

Original languageEnglish (US)
JournalPharmacogenomics Journal
DOIs
StateAccepted/In press - Sep 8 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

Krajinovic, M., Elbared, J., Drouin, S., Bertout, L., Rezgui, A., Ansari, M., Raboisson, M. J., Lipshultz, S. E., Silverman, L. B., Sallan, S. E., Neuberg, D. S., Kutok, J. L., Laverdière, C., Sinnett, D., & Andelfinger, G. (Accepted/In press). Polymorphisms of ABCC5 and NOS3 genes influence doxorubicin cardiotoxicity in survivors of childhood acute lymphoblastic leukemia. Pharmacogenomics Journal. https://doi.org/10.1038/tpj.2015.63