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Association of NADPH oxidase polymorphisms with anthracycline-induced cardiotoxicity in the RICOVER-60 trial of patients with aggressive CD20+ B-cell lymphoma

    Annegret Reichwagen

    Department of Pharmacology, Universitätsmedizin Mainz, Obere Zahlbacher Str. 67, 55101 Mainz, Germany

    Authors contributed equally

    Search for more papers by this author

    ,
    Marita Ziepert

    Institute for Medical Informatics, Statistics & Epidemiology, University of Leipzig, Germany

    Authors contributed equally

    Search for more papers by this author

    ,
    Markus Kreuz

    Institute for Medical Informatics, Statistics & Epidemiology, University of Leipzig, Germany

    ,
    Ute Gödtel-Armbrust

    Department of Pharmacology, Universitätsmedizin Mainz, Obere Zahlbacher Str. 67, 55101 Mainz, Germany

    ,
    Tanja Rixecker

    Internal Medicine, Saarland University Medical School, Saarland University, Homburg, Germany

    ,
    Viola Poeschel

    Internal Medicine, Saarland University Medical School, Saarland University, Homburg, Germany

    ,
    Mohammad Reza Toliat

    Cologne Center for Genomics, University of Cologne, Cologne, Germany

    ,
    Peter Nürnberg

    Cologne Center for Genomics, University of Cologne, Cologne, Germany

    ,
    Mladen Tzvetkov

    Department of Clinical Pharmacology, University Medical Center, Göttingen, Germany

    ,
    Shiwei Deng

    Department of Pharmacology, Universitätsmedizin Mainz, Obere Zahlbacher Str. 67, 55101 Mainz, Germany

    ,
    Lorenz Trümper

    Department of Hematology & Oncology, Medical Center of the Georg-August-University Göttingen, Germany

    ,
    Gerd Hasenfuss

    Department of Cardiology & Pneumology, Heart Research Center, Georg-August-University Göttingen, Germany

    ,
    Michael Pfreundschuh

    Internal Medicine, Saarland University Medical School, Saarland University, Homburg, Germany

    &
    Leszek Wojnowski

    *Author for correspondence:

    E-mail Address: wojnowski@uni-mainz.de

    Department of Pharmacology, Universitätsmedizin Mainz, Obere Zahlbacher Str. 67, 55101 Mainz, Germany

    Published Online:https://doi.org/10.2217/pgs.14.179

    Aim: To identify gene variants responsible for anthracycline-induced cardiotoxicity. Patients & methods: Polymorphisms of the NADPH oxidase subunits and of the anthracycline transporters ABCC1, ABCC2 and SLC28A3 were genotyped in elderly patients (61–80 years) treated for aggressive CD20+ B-cell lymphomas with CHOP-14 with or without rituximab and followed up for 3 years. Results: The accumulation of RAC2 subunit genotypes TA/AA among cases was statistically significant upon adjustment for gender, age and doxorubicin dose in a multivariate logistic regression analysis (OR: 2.3, p = 0.028; univariate: OR: 1.8, p = 0.077). RAC2 and CYBA genotypes were significantly associated with anthracycline-induced cardiotoxicity in a meta-analysis of this and a similar previous study. Conclusion: Our results support the theory that NADPH oxidase is involved in anthracycline-induced cardiotoxicity.

    Original submitted 9 July 2014; Revision submitted 19 December 2014

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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