TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

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; ... (2021). TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study. NPJ precision oncology, 5(1), p. 64. Springer Nature 10.1038/s41698-021-00178-z

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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.

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