학술논문
TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
Document Type
article
Author
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
Source
npj Precision Oncology, Vol 5, Iss 1, Pp 1-8 (2021)
Subject
Language
English
ISSN
2397-768X
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.