Association of NADPH oxidase polymorphisms with anthracycline-induced cardiotoxicity in the RICOVER-60 trial of patients with aggressive CD20+ B-cell lymphoma. (March 2015)

• Record Type: Journal Article
• Authors: Reichwagen, Annegret; Ziepert, Marita; Kreuz, Markus; Gödtel-Armbrust, Ute; Rixecker, Tanja; Poeschel, Viola; Reza Toliat, Mohammad; Nürnberg, Peter; Tzvetkov, Mladen; Deng, Shiwei; Trümper, Lorenz; Hasenfuss, Gerd; Pfreundschuh, Michael; Wojnowski, Leszek
• Is Part Of: Pharmacogenomics. Volume 16:Number 4(2015)
• Page Start: 361
• Page End: 372
• Publication Date: 2015-03
• Subjects: anthracyclines -- cardiotoxicity -- clinical trial -- heart failure -- RICOVER-60 -- SNP; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.14.179
• Languages: English
• ISSNs: 1462-2416

Abstract

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