PhD Scientific Days 2017

Oral Presentations: Oncology

Cardiotoxicity of anthracyclines in pediatric patients with cancer

Előadó neve

Dr. C. Sági, Judit

Előadó munkahelye

Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary

Előadó telefonszáma

(1) 210 2930 / 56502, +36206632868

Előadó e-mail címe

sjudit08@gmail.com

Az előadás címe

Cardiotoxicity of anthracyclines in pediatric patients with cancer

Szerző(k) neve és munkahelye

Judit Csányiné Sági 1, Bálint Egyed 1,2; Nóra Kutszegi 1,2; Andrea Kelemen 1, Gábor T. Kovács 2, Csaba Szalai 1,3; Dániel János Erdélyi 2, Ágnes Félné Semsei 1
1 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary;
2 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary;
3 Heim Pal Children Hospital, Budapest, Hungary;

Szekció

Oral Presentations: Oncology

Data of the presenter

Doctoral School: Molecular Medicine,
Program: Basis of Human Molecular Genetics and Gene Diagnostics
Supervisor: dr. Ágnes Félné Semsei
E-mail address: sjudit08@gmail.com

Oral presentation in Hungarian

Text of the abstract

Introduction: The survival rate of pediatric acute lymphoblastic leukemia (ALL) and osteosarcoma (OSC) improved remarkably with the development of chemotherapy. However, many adverse effects occur during or even years after treatment. There are a high inter-individual variability in their occurrence and severity; therefore, it is assumed that their formation is affected by the genetic background of the individuals. One of the adverse effects is anthracycline-induced cardiotoxicity (ACT).
Aims: Our goal was to investigate the pharmacogenetics of ACT in pediatric ALL and OSC patients.
Method: Patients are routinely monitored for cardiac functions during and after treatment. We collected echocardiography data from medical records of ALL and OSC patients retrospectively. Ejection fraction (EF) and fractional shortening (FS) of 661 patients was computed, FS was abnormal under the threshold 28 %. We categorized the length of the follow-up into eight categories. All together 67 single nucleotide polymorphisms (SNPs) were determined in 21 genes of xenobiotic transporters and anthracycline metabolizing enzymes. DNA was isolated from whole blood collected from patients in remission using QIAmpBlood DNA Maxi Kit. Genotyping was performed using TaqMan® OpenArray™ Genotyping System (Thermo Fisher Scientific). Multivariate general linear model and logistic regression adjusted for potential confounders was performed in the follow-up and in the case-control studies using the SPSS 23 software. P values < 0.005 were considered significant.
Results: Our results indicate that polymorphisms in ABCC2 and CYP3A5 genes may influence the cardiac parameters. Patients with ABCC2 rs3740066 GG genotype had decreased FS during the therapy containing also anthracyclines and 5-10 years after therapy (p=0.001, p=0.008, respectively). CYP3A5 rs4646450 T allele in males predisposed for abnormal FS (p=0.005).
Conclusion: Individualized chemotherapy based on genetic profiling may help to optimize anthracycline dosing leading to improvements in clinical outcome and reduced toxicity.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1117

Authors (legacy)

Judit Csányiné Sági 1, Bálint Egyed 1,2; Nóra Kutszegi 1,2; Andrea Kelemen 1, Gábor T. Kovács 2, Csaba Szalai 1,3; Dániel János Erdélyi 2, Ágnes Félné Semsei 1
1 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary;
2 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary;
3 Heim Pal Children Hospital, Budapest, Hungary;