title: Association of NADPH oxidase polymorphisms with anthracycline-induced cardiotoxicity in the RICOVER-60 trial of patients with aggressive CD20(+) B-cell lymphoma.
abstract: OBJECTIVE
  To identify gene variants responsible for anthracycline-induced cardiotoxicity.
  
  
  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.
  
  
  CONCLUSIONS
  Our results support the theory that NADPH oxidase is involved in anthracycline-induced cardiotoxicity. Original submitted 9 July 2014; Revision submitted 19 December 2014.
authors.affiliation: Department of Pharmacology, Universitätsmedizin Mainz, Obere Zahlbacher Str. 67, 55101 Mainz, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Reichwagen
authors.forename: Marita
authors.initials: M
authors.lastname: Ziepert
authors.forename: Markus
authors.initials: M
authors.lastname: Kreuz
authors.forename: Ute
authors.initials: U
authors.lastname: Gödtel-Armbrust
authors.forename: Tanja
authors.initials: T
authors.lastname: Rixecker
authors.forename: Viola
authors.initials: V
authors.lastname: Poeschel
authors.forename: Mohammad
authors.initials: M
authors.lastname: Reza Toliat
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Mladen
authors.initials: M
authors.lastname: Tzvetkov
authors.forename: Shiwei
authors.initials: S
authors.lastname: Deng
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Leszek
authors.initials: L
authors.lastname: Wojnowski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D066126:Cardiotoxicity / Q000235:genetics* / Q000473:pathology; D003520:Cyclophosphamide / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D019255:NADPH Oxidases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000009:adverse effects; D000069283:Rituximab / Q000009:adverse effects; D014750:Vincristine / Q000009:adverse effects; D020744:rac GTP-Binding Proteins / Q000235:genetics*; D000097766:RAC2 GTP-Binding Protein
chemical_list: D018943:Anthracyclines; D003520:Cyclophosphamide; D004317:Doxorubicin; D000089762:Multidrug Resistance-Associated Protein 2; D019255:NADPH Oxidases; D011241:Prednisone; D000069283:Rituximab; D014750:Vincristine; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C000715087:ABCC2 protein, human; C086986:CYBA protein, human
keywords: RICOVER-60; SNP; anthracyclines; cardiotoxicity; clinical trial; heart failure