Universität zu Köln

Zolk, Oliver ORCID: 0000-0002-8220-3834, von dem Knesebeck, Annika, Graf, Norbert ORCID: 0000-0002-2248-323X, Simon, Thorsten ORCID: 0000-0002-3425-8451, Hero, Barbara, Abdul-Khaliq, Hashim, Abd El Rahman, Mohamed, Spix, Claudia ORCID: 0000-0002-2123-9315, Mayer, Benjamin, Elsner, Susanne, Gebauer, Judith and Langer, Thorsten (2022). 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. JMIR RES. Protoc., 11 (2). TORONTO: JMIR PUBLICATIONS, INC. ISSN 1929-0748

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zolk, Oliver UNSPECIFIED orcid.org/0000-0002-8220-3834 UNSPECIFIED von dem Knesebeck, Annika UNSPECIFIED UNSPECIFIED UNSPECIFIED Graf, Norbert UNSPECIFIED orcid.org/0000-0002-2248-323X UNSPECIFIED Simon, Thorsten UNSPECIFIED orcid.org/0000-0002-3425-8451 UNSPECIFIED Hero, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Abdul-Khaliq, Hashim UNSPECIFIED UNSPECIFIED UNSPECIFIED Abd El Rahman, Mohamed UNSPECIFIED UNSPECIFIED UNSPECIFIED Spix, Claudia UNSPECIFIED orcid.org/0000-0002-2123-9315 UNSPECIFIED Mayer, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Elsner, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, Judith UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-687925
DOI:	10.2196/27898
Journal or Publication Title:	JMIR RES. Protoc.
Volume:	11
Number:	2
Date:	2022
Publisher:	JMIR PUBLICATIONS, INC
Place of Publication:	TORONTO
ISSN:	1929-0748
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANTHRACYCLINE CARDIOTOXICITY; HEART-FAILURE; CANCER; ASSOCIATION; MORTALITY; TOXICITY; VARIANT Multiple languages Health Care Sciences & Services; Public, Environmental & Occupational Health Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68792