| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
npj Precision Oncology, Vol 5, Iss 1, Pp 1-8 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2397-768X |
| DOI: |
10.1038/s41698-021-00178-z |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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