Abstract
| Original language | English |
|---|---|
| Article number | 64 |
| Journal | npj Precision Oncology |
| Volume | 5 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Dec 2021 |
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TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study. / The PanCareLIFE Consortium; and the CPNDS Consortium.
In: npj Precision Oncology, Vol. 5, No. 1, 64, 01.12.2021.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
AU - Meijer, A. J. M.
AU - Diepstraten, F. A.
AU - Langer, T.
AU - Broer, L.
AU - Domingo, I. K.
AU - Clemens, E.
AU - Uitterlinden, A. G.
AU - de Vries, A. C. H.
AU - van Grotel, M.
AU - Vermeij, W. P.
AU - Ozinga, R. A.
AU - Binder, H.
AU - Byrne, J.
AU - van Dulmen-den Broeder, E.
AU - Garrè, M. L.
AU - Grabow, D.
AU - Kaatsch, P.
AU - Kaiser, M.
AU - Kenborg, L.
AU - Winther, J. F.
AU - Rechnitzer, C.
AU - Hasle, H.
AU - Kepak, T.
AU - Kepakova, K.
AU - Tissing, W. J. E.
AU - van der Kooi, A. L. F.
AU - Kremer, L. C. M.
AU - Kruseova, J.
AU - Pluijm, S. M. F.
AU - Kuehni, C. E.
AU - van der Pal, H. J. H.
AU - Parfitt, R.
AU - Spix, C.
AU - Tillmanns, A.
AU - Deuster, D.
AU - Matulat, P.
AU - Calaminus, G.
AU - Hoetink, A. E.
AU - Elsner, S.
AU - Gebauer, J.
AU - Haupt, R.
AU - Lackner, H.
AU - Blattmann, C.
AU - Neggers, S. J. C. M. M.
AU - Rassekh, S. R.
AU - Wright, G. E. B.
AU - Brooks, B.
AU - Nagtegaal, A. P.
AU - Drögemöller, B. I.
AU - Ross, C. J. D.
AU - The PanCareLIFE Consortium
AU - Bhavsar, A. P.
AU - am Zehnhoff-Dinnesen, A. G.
AU - Carleton, B. C.
AU - and the CPNDS Consortium
AU - Zolk, O.
AU - van den Heuvel-Eibrink, M. M.
AU - de Vries, A. C. H.
AU - van Grotel, M.
AU - van Dulmen-den Broeder, E.
AU - van der Kooi, A. L. F.
AU - Kremer, L. C. M.
AU - van der Pal, H. J. H.
AU - Calaminus, G.
AU - van den Heuvel-Eibrink, M. M.
N1 - Funding Information: We would like to thank all childhood cancer patients and their families for their contribution to this study. PanCareLIFE (PCL) is a collaborative project in the 7th Framework Program of the European Union. PCL partners for this project are University Medical Center Mainz, Germany (P.K., D.G.), Boyne Research Institute, Drogheda, Ireland (J.B., H. Campbell), Pintail Ltd., Dublin, Ireland (Mr. C. Clissmann, Dr. K. O’Brien), Amsterdam University Medical Centers, University of Amsterdam, Netherlands (L.C.M.K.), University of Lübeck, Germany (T.L.), Amsterdam University Medical Centers, VU Medical Center, Netherlands (Dr. E. van Dulmen-den Broeder, M.H. van den Berg), Erasmus Medical Center Rotterdam, Netherlands (M.M.H.E.), Charité Hospital Berlin, Germany (Professor A. Borgmann-Staudt, Mr. R. Schilling), University of Münster, Germany (A.G.Z.D.), University of Bern, Switzerland (C.E.K.), IRCCS Istituto Giannina Gaslini, Genova, Italy (R.H., Dr. F. Bagnasco), University Hospital Brno, Czech Republic (T.K.), University Hospital Saint Etienne, France (Dr. C. Berger, Dr. L. Casagranda), Danish Cancer Society, Copenhagen, Denmark (J.F.W.), Motol University Hospital, Prague, Czech Republic (J.K.), and University Hospital Bonn, Germany (G.C., K.B.). Discovery cohort data in PCL were provided by: Erasmus Medical Center, Netherlands (M.M.H.E.), Princess Máxima Center for Pediatric Oncology, Netherlands (M.M.H.E.), University Medical Center Groningen, Netherlands (W.J.E.T.), Amsterdam University Medical Centers, University of Amsterdam, Netherlands (L.C.M. K.), University of Munster, Germany (A.G.Z.D., Professor U. Dirksen), University of Bern, Switzerland (C.E.K.), IRCCS Istituto Giannina Gaslini, Genova, Italy (R.H., M.L.G.), The University Hospital Brno, Czech Republic (T.K.), Danish Cancer Society, Copenhagen, Denmark (J.F.W.), Motol University Hospital, Prague, Czech Republic (J.K.), Medical University of Graz, Austria (H.L.), Ulm University, Germany (Professor H. Cario, O.Z.), University of Lübeck, Germany (T.L.), Klinikum Stuttgart, Olgahospital, Germany (Professor S. Bielack), and University Hospital Bonn, Germany (G.C.). Replication cohort 1 data were provided by Canadian Pharmacogenomics Network for Drug Safety (CPNDS) Consortium (Vancouver, British Columbia Children’s Hospital, B.C.C., C.J.D.R., S.R.R.; Edmonton, University of Alberta, A.P.B., D.E.; Calgary, Alberta Children’s Hospital, G Guilcher; Winnipeg Health Sciences Centre, J.M., G.’t.J, G.C.; London Health Sciences Centre, M.R.; Toronto, Hospital for Sick Children: S.I., P.N.; Ottawa, Children’s Hospital of Eastern Ontario, R.V., D.J.; Montreal, CHU Sainte‐Justine, J.-F.B., D.L.; Montreal Children’s Hospital, N.J.; Halifax, IWK Health Centre, K.G., K.K.). Replication cohort 2 data were provided by Ulm University, Germany (O.Z.). Age-related hearing loss data were provided by the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, Erasmus Medical Center, Netherlands (A.P.N.). Functional validation experiments were performed at the Department of Medical Microbiology and Immunology, University of Alberta, Canada (A.P.B.), and at the Princess Máxima Center for Pediatric Oncology, Netherlands (W.P.V.). This work was supported by the PanCareLIFE project that has received funding from the European Union’s Seventh Framework Program for research, technological development and demonstration under grant agreement no 602030. AM is supported by Stichting Gaby Olthuis Fonds, the Netherlands, under Grant number 2020-003. Functional studies have been supported by funding from the Canadian Institutes of Health Research; PJT-153145 and MY2-155361 to A.B., C.R., and B.C. and recruitment funding from the University of Alberta Li Ka Shing Institute of Virology and Faculty of Medicine & Dentistry to AB, and Oncode to WV and RO. AB holds a (Tier 2) Canada Research Chair (231622) in Functional Genomic Medicine and this research was undertaken, in part, thanks to funding from the Canada Research Chairs Program. This research has also been funded by the generous support of the Stollery Children’s Hospital Foundation through the Women and Children’s Health Research Institute to AB. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85117051914&partnerID=8YFLogxK
U2 - 10.1038/s41698-021-00178-z
DO - 10.1038/s41698-021-00178-z
M3 - Article
C2 - 34262104
VL - 5
JO - npj Precision Oncology
JF - npj Precision Oncology
SN - 2397-768X
IS - 1
M1 - 64
ER -