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Titel: Cardiovascular Health Status And Genetic Risk In Survivors of Childhood Neuroblastoma and Nephroblastoma Treated With Doxorubicin: Protocol of the Pharmacogenetic Part of the LESS-Anthra Cross-Sectional Cohort Study
VerfasserIn: Zolk, Oliver
von dem Knesebeck, Annika
Graf, Norbert
Simon, Thorsten
Hero, Barbara
Abdul-Khaliq, Hashim
Abd El Rahman, Mohamed
Spix, Claudia
Mayer, Benjamin
Elsner, Susanne
Gebauer, Judith
Langer, Thorsten
Sprache: Englisch
Titel: JMIR Research Protocols
Bandnummer: 11
Heft: 2
Verlag/Plattform: JMIR Publications
Erscheinungsjahr: 2022
Freie Schlagwörter: cardiotoxicity
anthracyclines
childhood cancer survivors
genetics
polymorphisms
cardiology
cardiac health
cancer
survivors
childhood
children
risk monitoring
genetics
cardiovascular health
pediatrics
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Background: In childhood cancer survivors (survival of 5 years or more after diagnosis), cardiac toxicity is the most common nonmalignant cause of death attributed to treatment-related consequences. Identifying patients at risk of developing late cardiac toxicity is therefore crucial to improving treatment outcomes. The use of genetic markers has been proposed, together with clinical risk factors, to predict individual risk of cardiac toxicity from cancer therapies, such as doxorubicin. Objective: The primary aim of this study is to evaluate the value of multimarker genetic testing for RARG rs2229774, UGT1A6 rs17863783, and SLC28A3 rs7853758 for predicting doxorubicin-induced cardiotoxicity. The secondary aim is to replicate previously described associations of candidate genetic markers with doxorubicin-induced cardiotoxicity. Moreover, we will evaluate the prevalence of cardiovascular dysfunction in childhood cancer survivors after neuroblastoma or nephroblastoma. Methods: This is the pharmacogenetic substudy of the research project Structural Optimization for Children With Cancer After Anthracycline Therapy (LESS-Anthra). We invited 2158 survivors of childhood neuroblastoma or nephroblastoma treated with doxorubicin according to the trial protocols of SIOP 9/GPOH, SIOP 93-01/GPOH, SIOP 2001/GPOH, NB 90, NB 97, or NB 2004 to participate in this prospective cross-sectional cohort study. The study participants underwent a cardiological examination and were asked to provide a blood or saliva sample for genotyping. The study participants' health statuses and cardiovascular diagnoses were recorded using a questionnaire completed by the cardiologist. Digital echocardiographic data were centrally evaluated to determine the contractile function parameters. Medical data on the tumor diagnosis and treatment protocol were taken from the study documentation. Survivors were screened for variants of several candidate genes by TaqMan genotyping. Results: This study includes 657 survivors treated with doxorubicin for childhood cancer, the largest German cohort assembled to date to investigate cardiovascular late effects. Data analyses are yet to be completed. Conclusions: This study will define the genetic risk related to 3 marker genes proposed in a pharmacogenetic guideline for risk assessment. Moreover, the results of this study will show the prevalence of cardiovascular dysfunction in survivors of pediatric neuroblastoma or nephroblastoma who were treated with doxorubicin. The results will help to improve primary treatment and follow-up care, thus reducing cardiovascular late effects in the growing population of childhood cancer survivors.
DOI der Erstveröffentlichung: 10.2196/27898
URL der Erstveröffentlichung: https://www.researchprotocols.org/2022/2/e27898
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-406214
hdl:20.500.11880/36498
http://dx.doi.org/10.22028/D291-40621
ISSN: 1929-0748
Datum des Eintrags: 27-Sep-2023
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Pädiatrie
Professur: M - Prof. Dr. Norbert Graf
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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