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TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
- Source :
- Meijer , A J M , Diepstraten , F A , Langer , T , Broer , L , Domingo , I K , Clemens , E , Uitterlinden , A G , de Vries , A C H , van Grotel , M , Vermeij , W P , Ozinga , R A , Binder , H , Byrne , J , van Dulmen-den Broeder , E , Garrè , M L , Grabow , D , Kaatsch , P , Kaiser , M , Kenborg , L , Winther , J F , Rechnitzer , C , Hasle , H , Kepak , T , Kepakova , K , Tissing , W J E , van der Kooi , A L F , Kremer , L C M , Kruseova , J , Pluijm , S M F , Kuehni , C E , van der Pal , H J H , Parfitt , R , Spix , C , Tillmanns , A , Deuster , D , Matulat , P , Calaminus , G , Hoetink , A E , Elsner , S , Gebauer , J , Haupt , R , Lackner , H , Blattmann , C , Neggers , S J C M M , Rassekh , S R , Wright , G E B , Brooks , B , Nagtegaal , A P , Drögemöller , B I , Ross , C J D , the PanCareLIFE Consortium & and the CPNDS Consortium 2021 , ' TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study ' , npj Precision Oncology , vol. 5 , 64 .
- Publication Year :
- 2021
-
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.
Details
- Database :
- OAIster
- Journal :
- Meijer , A J M , Diepstraten , F A , Langer , T , Broer , L , Domingo , I K , Clemens , E , Uitterlinden , A G , de Vries , A C H , van Grotel , M , Vermeij , W P , Ozinga , R A , Binder , H , Byrne , J , van Dulmen-den Broeder , E , Garrè , M L , Grabow , D , Kaatsch , P , Kaiser , M , Kenborg , L , Winther , J F , Rechnitzer , C , Hasle , H , Kepak , T , Kepakova , K , Tissing , W J E , van der Kooi , A L F , Kremer , L C M , Kruseova , J , Pluijm , S M F , Kuehni , C E , van der Pal , H J H , Parfitt , R , Spix , C , Tillmanns , A , Deuster , D , Matulat , P , Calaminus , G , Hoetink , A E , Elsner , S , Gebauer , J , Haupt , R , Lackner , H , Blattmann , C , Neggers , S J C M M , Rassekh , S R , Wright , G E B , Brooks , B , Nagtegaal , A P , Drögemöller , B I , Ross , C J D , the PanCareLIFE Consortium & and the CPNDS Consortium 2021 , ' TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study ' , npj Precision Oncology , vol. 5 , 64 .
- Notes :
- application/pdf, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1322768171
- Document Type :
- Electronic Resource