Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Meijer, AJM; Diepstraten, FA; Langer, T; Broer, L; Domingo, IK; Clemens, E; Uitterlinden, AG; de Vries, ACH; van Grotel, M; Vermeij, WP; Ozinga, RA; Binder, H; Byrne, J; van Dulmen-den Broeder, E; Garre, ML; Grabow, D; Kaatsch, P; Kaiser, M; Kenborg, L; Winther, JF; Rechnitzer, C; Hasle, H; Kepak, T; Kepakova, K; Tissing, WJE; van der Kooi, ALF; Kremer, LCM; Kruseova, J; Pluijm, SMF; Kuehni, CE; van der Pal, HJH; Parfitt, R; Spix, C; Tillmanns, A; Deuster, D; Matulat, P; Calaminus, G; Hoetink, AE; Elsner, S; Gebauer, J; Haupt, R; Lackner, H; Blattmann, C; Neggers, SJCMM; Rassekh, SR; Wright, GEB; Brooks, B; Nagtegaal, AP; Drogemoller, BI; Ross, CJD; Bhavsar, AP; Zehnhoff-Dinnesen, AGA; Carleton, BC; Zolk, O; van den Heuvel-Eibrink, MM.
TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
NPJ PRECIS ONCOL. 2021; 5(1): 64
Doi: 10.1038/s41698-021-00178-z
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- Co-Autor*innen der Med Uni Graz
- Lackner Herwig
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- 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 x 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.