Association between genetic polymorphisms and platinum-induced ototoxicity in children.
Fiche publication
Date publication
juillet 2018
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHASTAGNER Pascal, Pr ENTZ-WERLE Natacha
Tous les auteurs :
Lui G, Bouazza N, Denoyelle F, Moine M, Brugières L, Chastagner P, Corradini N, Entz-Werle N, Vérité C, Landmanparker J, Sudour-Bonnange H, Pasquet M, Verschuur A, Faure-Conter C, Doz F, Tréluyer JM
Lien Pubmed
Résumé
Platinum is extensively used in the treatment of several childhood cancers. However, ototoxicity is one of the most notable adverse effects, especially in children. Several studies suggest that genetics may predict its occurrence. Here, polymorphisms associated with platinum-induced ototoxicity were selected from the literature and were investigated in a pediatric population treated with platinum-based agents. In this retrospective study, patients treated with cisplatin and/or carboplatin were screened. The patients with pre- and post-treatment audiogram (Brock criteria) available were included. We selected polymorphisms that have previously been associated with cisplatin ototoxicity with a minor allele frequency ≥30%. Deletion of and , rs1799735 (), rs1695 (), rs4880 (), rs2228001 (), rs1799793 () and rs4788863 () were investigated. Data of one hundred and six children matching the eligible criteria were analyzed. Thirty-three patients (31%) developed ototoxicity (with a Brock grade ≥2). The probability of hearing loss increased significantly in patients carrying the null genotype for (P = 0.03), A/A genotype at rs1695 (P = 0.01), and C/C genotype at rs1799793 (P = 0.008). We also showed an association of the cumulative doses of carboplatin with cisplatin ototoxicity (P <0.05). To conclude, deletion of , rs1695 and rs1799793 may constitute potential predictors of platinum-induced ototoxicity.
Mots clés
cancer, children, ototoxicity, pharmacogenetics, platinum
Référence
Oncotarget. 2018 Jul 20;9(56):30883-30893