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Metadata record for the article: TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
online resource
posted on 2021-04-22, 14:21 authored by Annelot Meijer, Franciscus Diepstraten, Thorsten Langer, Linda Broer, Ivan Domingo, Eva Clemens, André Uitterlinden, Andrica de vries, Martine van Grotel, Wilbert Vermeij, Rutger Ozinga, Harald Binder, Julianne Byrne, Eline van Dulmen-den Broeder, Maria Luisa Garrè, Desiree Grabow, Peter Kaatsch, Melanie Kaiser, Line Kenborg, Jeanette Falck Winther, Catherine Rechnitzer, Henrik Hasle, Tomas Kepak, Katerina Kepakova, Wim Tissing, Anne-Lotte L. F. van der Kooi, Leontien Kremer, Jarmila Kruseova, Saskia Pluijm, Claudia Kuehni, Helena van der Pal, Ross Parfitt, Claudia Spix, Amélie Tillmanns, Dirk Deuster, Peter Matulat, Gabriele Calaminus, Alex Hoetink, Susanne Elsner, Judith Gebauer, Riccardo Haupt, Herwig Lackner, Claudia Blattmann, Sebastian Neggers, Shahrad Rassekh, Galen Wright, Beth Brooks, Andries Nagtegaal, Britt Drögemöller, Colin Ross, Amit Bhavsar, Antoinette am Zehnhoff-Dinnesen, Bruce Carleton, Oliver Zolk, Marry van den Heuvel-EibrinkThis metadata record provides details of the data supporting the claims of the related article: “TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study”.
The related study used a genome-wide association (GWAS) approach to investigate genetic susceptibility to cisplatin-induced ototoxicity in paediatric cancer patients. The study identified a genetic variant in the gene TCERG1L (rs893507) as being associated with hearing loss in this patient cohort.
Type of data: GWAS summary statistics; Mus musculus gene expression data
Subject of data: Homo sapiens - cisplatin-treated, non-cranial irradiated patients
Sample size: 390 participants
Population characteristics:
PCL discovery cohort (n=390): median age at diagnosis 11.1 years (0.0-18.8); median age at audiological testing 11.8 years (0.3-19.0); median total cumulative dose cisplatin 480 mg/m2 (range: 40-950 mg/m2). 76 (19.5%) patients had been treated with additional carboplatin. 168 (43.1%) patients developed Muenster ≥2b hearing loss.
Canadian first replication cohort (n=192): median age at diagnosis 4.1 years (0.1-18.8); median cumulative dose cisplatin 400 mg/m2 (300-480 mg/m2). 115 patients (59.9%) developed Muenster ≥2b hearing loss.
PCL second replication cohort (n=188): median age at diagnosis 11.1 years (0.3-18.0); median cumulative dose of cisplatin 480 mg/m2 (83-770); 94 survivors (50%) developed Muenster ≥2b hearing loss.
Recruitment: PCL discovery cohort and PCL second replication cohort: Study participants were recruited through the PCL network consisting of 14 institutions from 7 countries: Switzerland, Italy, Czech Republic, Denmark, Germany, Austria, and the Netherlands.
Canadian children replication cohort: participants were recruited via the Canadian Pharmacogenomics Network for Drug Safety (CPNDS), a national research and patients care network established to reduce serious adverse drug reactions in children.
Data for this study was collected prospectively as well as retrospectively. Selection bias could have occurred in the retrospective collection of data. As a result of missing or unclassifiable audiograms, some patients could not be included due to a missing phenotype. Because many of the patients with missing audiograms might have had good hearing function, they might therefore no longer had follow-up(s) for audiometric testing, As a consequence, the odds of ototoxicity based on the results of this study could have been slightly overestimated.
Date of data collection: January 2015 to October 2017
Geographic location: Netherlands; Canada; Germany
Data access
Summary statistics from GWAS analyses of participant blood and saliva samples (Meijer_01032021_cisplatin_induced_hearing_loss.tsv) are openly available from the GWAS Catalog: https://www.ebi.ac.uk/gwas/studies/GCST90013831.
Gene expression profiling data from mouse tissues in response to cisplatin treatment, are openly available from Gene Expression Omnibus: https://identifiers.org/geo:GSE117167.
Further data from this study cannot be made openly available due to restrictions based on privacy regulations and informed consent of the participants in Europe and Canada. Requests for data access should be sent to the principal investigator of each cohort.
Corresponding authors for this study
MM van den Heuvel-Eibrink (m.m.vandenheuvel-eibrink@prinsesmaximacentrum.nl) – PCL discovery cohort
Bruce Carleton (bcarleton@popi.ubc.ca) – Canadian replication cohort
Oliver Zolk (Oliver.Zolk@mhb-fontane.de) – PCL replication cohort
Andries Nagtegaal (a.nagtegaal@erasmusmc.nl) - CHARGE cohort
Study approval
The PanCareLIFE study was approved by the local ethics committees:
• Kantonale Ethikkommission Bern, 362/2015
• Comitate Etico Regionale, 507REG2014
• Ethical Committee University Hospital Brno, June 11, 2016
• Ethics Committee Fakultni Nemocnice v Motole Prague, EK-1447/14
• De Videnskabsetiske Komiteer Region Hovedstaden, H-1-2014-125
• Ethikkommission Medizinische Universität Graz, 27-015 ex 14/15
• Ethikkommission der Universität Ulm, 160/17
• Ethikkommission der Universität zu Lübeck, 14/181
• Ethik-Kommission der Ärztekammer Westfalen-Lippe und der Westfälischen Wilhelms-Universität Münster, 2014-619
• Medische Ethische Toetsings Commissie Erasmus MC, MEC-2014-633
• Medisch Ethische Toetsingscommissie, 2015_202
European Union Seventh Framework Programme (602030)
CPNDS studies were approved by the Canadian Research Ethics Board (i H04-70358)
All participants provided written informed consent to participate in the study and to have their information obtained from treating physicians.
