npj Precision Oncology (Jul 2021)
TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
- A. J. M. Meijer,
- F. A. Diepstraten,
- T. Langer,
- L. Broer,
- I. K. Domingo,
- E. Clemens,
- A. G. Uitterlinden,
- A. C. H. de Vries,
- M. van Grotel,
- W. P. Vermeij,
- R. A. Ozinga,
- H. Binder,
- J. Byrne,
- E. van Dulmen-den Broeder,
- M. L. Garrè,
- D. Grabow,
- P. Kaatsch,
- M. Kaiser,
- L. Kenborg,
- J. F. Winther,
- C. Rechnitzer,
- H. Hasle,
- T. Kepak,
- K. Kepakova,
- W. J. E. Tissing,
- A. L. F. van der Kooi,
- L. C. M. Kremer,
- J. Kruseova,
- S. M. F. Pluijm,
- C. E. Kuehni,
- H. J. H. van der Pal,
- R. Parfitt,
- C. Spix,
- A. Tillmanns,
- D. Deuster,
- P. Matulat,
- G. Calaminus,
- A. E. Hoetink,
- S. Elsner,
- J. Gebauer,
- R. Haupt,
- H. Lackner,
- C. Blattmann,
- S. J. C. M. M. Neggers,
- S. R. Rassekh,
- G. E. B. Wright,
- B. Brooks,
- A. P. Nagtegaal,
- B. I. Drögemöller,
- C. J. D. Ross,
- A. P. Bhavsar,
- A. G. am Zehnhoff-Dinnesen,
- B. C. Carleton,
- O. Zolk,
- M. M. van den Heuvel-Eibrink,
- the PanCareLIFE Consortium,
- and the CPNDS Consortium
Affiliations
- A. J. M. Meijer
- Princess Máxima Center for Pediatric Oncology
- F. A. Diepstraten
- Princess Máxima Center for Pediatric Oncology
- T. Langer
- Department of Pediatric Oncology and Hematology, University Hospital for Children and Adolescents
- L. Broer
- Department of Internal Medicine, Erasmus Medical Center
- I. K. Domingo
- Department of Medical Microbiology and Immunology, University of Alberta
- E. Clemens
- Princess Máxima Center for Pediatric Oncology
- A. G. Uitterlinden
- Department of Internal Medicine, Erasmus Medical Center
- A. C. H. de Vries
- Princess Máxima Center for Pediatric Oncology
- M. van Grotel
- Princess Máxima Center for Pediatric Oncology
- W. P. Vermeij
- Princess Máxima Center for Pediatric Oncology
- R. A. Ozinga
- Princess Máxima Center for Pediatric Oncology
- H. Binder
- German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz
- J. Byrne
- Boyne Research Institute
- E. van Dulmen-den Broeder
- Princess Máxima Center for Pediatric Oncology
- M. L. Garrè
- Department of Neurooncology, IRCCS Istituto Giannina Gaslini
- D. Grabow
- German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz
- P. Kaatsch
- German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz
- M. Kaiser
- German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz
- L. Kenborg
- Childhood Cancer Research Group, Danish Cancer Society Research Center
- J. F. Winther
- Childhood Cancer Research Group, Danish Cancer Society Research Center
- C. Rechnitzer
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet
- H. Hasle
- Department of Pediatrics, Aarhus University Hospital
- T. Kepak
- University Hospital Brno
- K. Kepakova
- University Hospital Brno
- W. J. E. Tissing
- Princess Máxima Center for Pediatric Oncology
- A. L. F. van der Kooi
- Princess Máxima Center for Pediatric Oncology
- L. C. M. Kremer
- Princess Máxima Center for Pediatric Oncology
- J. Kruseova
- Department of Children Hemato-Oncology, Motol University Hospital Prague
- S. M. F. Pluijm
- Princess Máxima Center for Pediatric Oncology
- C. E. Kuehni
- Institute of Social and Preventive Medicine, University of Bern
- H. J. H. van der Pal
- Princess Máxima Center for Pediatric Oncology
- R. Parfitt
- Department of Phoniatrics and Pedaudiology, University Hospital Münster, Westphalian Wilhelm University
- C. Spix
- German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz
- A. Tillmanns
- Department of Phoniatrics and Pedaudiology, University Hospital Münster, Westphalian Wilhelm University
- D. Deuster
- Department of Phoniatrics and Pedaudiology, University Hospital Münster, Westphalian Wilhelm University
- P. Matulat
- Department of Phoniatrics and Pedaudiology, University Hospital Münster, Westphalian Wilhelm University
- G. Calaminus
- Pediatric Hematology and Oncology, University Children’s Hospital Muenster
- A. E. Hoetink
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Utrecht
- S. Elsner
- Institute of Social Medicine and Epidemiology, University of Lübeck
- J. Gebauer
- Department of Internal Medicine, University Hospital of Schleswig-Holstein, Campus Lübeck
- R. Haupt
- Epidemiology and Biostatistics Unit and DOPO Clinic, IRCCS Istituto Giannina Gaslini
- H. Lackner
- Department of Pediatric and Adolescent Medicine, Medical University of Graz
- C. Blattmann
- Department of Pediatric Oncology/Hematology/Immunology, Stuttgart Cancer Center, Olgahospital
- S. J. C. M. M. Neggers
- Princess Máxima Center for Pediatric Oncology
- S. R. Rassekh
- BC Children’s Hospital Research Institute
- G. E. B. Wright
- BC Children’s Hospital Research Institute
- B. Brooks
- Audiology and Speech Pathology Department, BC Children’s Hospital
- A. P. Nagtegaal
- Departement of Otorhinolaryngology, Erasmus Medical Center
- B. I. Drögemöller
- BC Children’s Hospital Research Institute
- C. J. D. Ross
- BC Children’s Hospital Research Institute
- A. P. Bhavsar
- Department of Medical Microbiology and Immunology, University of Alberta
- A. G. am Zehnhoff-Dinnesen
- Department of Phoniatrics and Pedaudiology, University Hospital Münster, Westphalian Wilhelm University
- B. C. Carleton
- BC Children’s Hospital Research Institute
- O. Zolk
- Institute of Clinical Pharmacology, Brandenburg Medical School
- M. M. van den Heuvel-Eibrink
- Princess Máxima Center for Pediatric Oncology
- the PanCareLIFE Consortium
- and the CPNDS Consortium
- DOI
- https://doi.org/10.1038/s41698-021-00178-z
- Journal volume & issue
-
Vol. 5,
no. 1
pp. 1 – 8
Abstract
Abstract 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.
