Abstract
BackgroundAnthracyclines are a mainstay of chemotherapy. However, a relatively frequent adverse outcome of anthracycline treatment is cardiomyopathy. Multiple genetic studies have begun to dissect the complex genetics underlying cardiac sensitivity to the anthracycline drug class. A number of single nucleotide polymorphisms (SNPs) have been identified to be in linkage disequilibrium with anthracycline induced cardiotoxicity in paediatric populations.MethodsHere we screened for the presence of SNPs resulting in a missense coding change in a cohort of children with early onset chemotherapy related cardiomyopathy. The SNP identity was evaluated by Sanger sequencing of PCR amplicons from genomic DNA of patients with anthracycline related cardiac dysfunction.ResultsAll of the published SNPs were observed within our patient group. There was no correlation between the number of missense variants an individual carried with severity of disease. Furthermore, the time to cardiac disease onset post-treatment was not greater in those individuals carrying a high load of SNPs resulting from missense variants.ConclusionsWe conclude that previously identified missense SNPs are present within a paediatric cohort with early onset heart damage induced by anthracyclines. However, these SNPs require further replication cohorts and functional validation before being deployed to assess anthracycline cardiotoxicity risk in the clinic.
Highlights
Twenty (20) patients were identified with severe are experiencing higher survivalAnthracycline cardiotoxicity (ACT) with a fractional shortening < 24% [32]
Of these fifteen consented to genetic analysis to assess the number of anthracycline cardiotoxicity associated Single nucleotide polymorphism (SNP) (Table 1)
In this study we have examined genetic variants previously associated with ACT in a cohort of severely affected paediatric patients
Summary
A relatively frequent adverse outcome of anthracycline treatment is cardiomyopathy. Symptomatic ACT is usually defined as congestive cardiac failure, whereas patients with subclinical cardiotoxicity remain asymptomatic. Large cohort studies have found that symptomatic ACT occurs in 1.7–9.8% of childhood cancer survivors [12, 13]. The prevalence of subclinical ACT is less certain, and has been reported to occur in 0 to 57% of childhood cancer survivors [14]. The most widely used criteria for assessing left ventricular subclinical cardiotoxicity is echocardiography, fractional shortening (FS) and ejection fraction (EF). These measures are dependent on preload, afterload and contractility and are a measure of systolic function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
