title: Potential genetic predisposition for anthracycline-associated cardiomyopathy in families with dilated cardiomyopathy.
abstract: Anthracyclines are successfully used in cancer treatment, but their use is limited by their cardiotoxic side effects. Several risk factors for anthracycline-associated cardiomyopathy (AACM) are known, yet the occurrence of AACM in the absence of these known risk factors suggests that other factors must play a role. The purpose of this study was to evaluate whether a genetic predisposition for dilated cardiomyopathy (DCM) could be a potential risk factor for AACM.
  
  
  
  A hospital-based registry of 162 DCM families and two hospital-based registries of patients with cancer treated with systemic cancer therapy (n>6000) were reviewed focusing on AACM. Selected patients with AACM/DCM families with possible AACM (n=21) were analysed for mutations in cardiomyopathy-associated genes and presymptomatic cardiological evaluation of first-degree relatives was performed.
  
  
  
  We identified five DCM families with AACM and one patient with AACM with a family member with a possible early sign of mild DCM. Pathogenic MYH7 mutations were identified in two of these six families. The MYH7 c.1633G>A (p.Asp545Asn) and c.2863G>A (p.Asp955Asn) mutations (one double mutant allele) were identified in a DCM family with AACM. The MYH7 c.4125T>A (p.Tyr1375X) mutation was identified in one patient with AACM.
  
  
  
  This study further extends the hypothesis that a genetic predisposition to DCM could be a potential risk factor for AACM.
authors.affiliation: Department of Genetics , University Medical Center Groningen, University of Groningen , Groningen , T he Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Wasielewski
authors.affiliation: Department of Genetics , University Medical Center Groningen, University of Groningen , Groningen , T he Netherlands ; Department of Clinical Genetics , Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands.
authors.forename: Karin Y
authors.initials: KY
authors.lastname: van Spaendonck-Zwarts
authors.affiliation: Department of Genetics , University Medical Center Groningen, University of Groningen , Groningen , T he Netherlands.
authors.forename: Nico-Derk L
authors.initials: ND
authors.lastname: Westerink
authors.affiliation: Department of Genetics , University Medical Center Groningen, University of Groningen , Groningen , T he Netherlands.
authors.forename: Jan D H
authors.initials: JD
authors.lastname: Jongbloed
authors.affiliation: Department of Paediatric Oncology , University Medical Center Groningen, University of Groningen, Beatrix Children's Hospital , Groningen , The Netherlands.
authors.forename: Aleida
authors.initials: A
authors.lastname: Postma
authors.affiliation: Department of Medical Oncology , University Medical Center Groningen, University of Groningen , Groningen , The Netherlands.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.affiliation: Department of Genetics , University Medical Center Groningen, University of Groningen , Groningen , T he Netherlands.
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
authors.affiliation: Department of Cardiology , University Medical Center Groningen, University of Groningen, Groningen , The Netherlands.
authors.forename: Maarten P
authors.initials: MP
authors.lastname: van den Berg
keywords: GENETICS