TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.
Annelot J M MeijerFranciscus A DiepstratenT LangerL BroerI K DomingoE ClemensAndre G UitterlindenA C H de VriesM van GrotelWilbert P VermeijR A OzingaH BinderJ ByrneE van Dulmen-den BroederM L GarrèD GrabowP KaatschM KaiserL KenborgJ F WintherC RechnitzerHenrik HasleTomáš KepákK KepakovaW J E TissingAnne-Lotte L F van der KooiL C M KremerJ KruseovaS M F PluijmClaudia Elisabeth KuehniH J H van der PalR ParfittC SpixA TillmannsD DeusterP MatulatG CalaminusAlexander E HoetinkS ElsnerJ GebauerR HauptH LacknerC BlattmannS J C M M NeggersS R RassekhG E B WrightB BrooksAndries Paul NagtegaalBritt I DrögemöllerColin J D RossA P BhavsarA G Am Zehnhoff-DinnesenBruce C CarletonOliver ZolkMarry M M van den Heuvel-Eibrinknull nullnull nullPublished in: NPJ precision oncology (2021)
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.