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