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TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
AJM. Meijer, FA. Diepstraten, T. Langer, L. Broer, IK. Domingo, E. Clemens, AG. Uitterlinden, ACH. de Vries, M. van Grotel, WP. Vermeij, RA. Ozinga, H. Binder, J. Byrne, E. van Dulmen-den Broeder, ML. Garrè, D. Grabow, P. Kaatsch, M. Kaiser, L....
Language English Country Great Britain
Document type Journal Article
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- Journal Article MeSH
In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10-10, OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.
Audiology and Speech Pathology Department BC Children's Hospital Vancouver BC Canada
BC Children's Hospital Research Institute Vancouver BC Canada
Boyne Research Institute Drogheda Ireland
Childhood Cancer Research Group Danish Cancer Society Research Center Copenhagen Denmark
Departement of Otorhinolaryngology Erasmus Medical Center Rotterdam The Netherlands
Department of Children Hemato Oncology Motol University Hospital Prague Prague Czech Republic
Department of Internal Medicine Erasmus Medical Center Rotterdam The Netherlands
Department of Medical Genetics University of Alberta Edmonton AB Canada
Department of Medical Microbiology and Immunology University of Alberta Edmonton AB Canada
Department of Neurooncology IRCCS Istituto Giannina Gaslini Genova Italy
Department of Pediatric and Adolescent Medicine Medical University of Graz Graz Austria
Department of Pediatric Oncology Academic Medical Center Amsterdam Amsterdam The Netherlands
Department of Pediatric Oncology Erasmus MC Sophia Children's Hospital Rotterdam The Netherlands
Department of Pediatrics Aarhus University Hospital Aarhus Denmark
Epidemiology and Biostatistics Unit and DOPO Clinic IRCCS Istituto Giannina Gaslini Genova Italy
Faculty of Pharmaceutical Sciences University of British Columbia British Columbia Canada
Institute of Clinical Pharmacology Brandenburg Medical School Rüdersdorf Germany
Institute of Social and Preventive Medicine University of Bern Bern Switzerland
Institute of Social Medicine and Epidemiology University of Lübeck Lübeck Germany
International Clinical Research Center Brno Czech Republic
Oncode Institute Utrecht The Netherlands
Pediatric Hematology and Oncology University Children's Hospital Muenster Muenster Germany
Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
References provided by Crossref.org
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