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Updated: Mar 24, 2026
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Replication of a genetic variant in ACYP2 associated with cisplatin-induced hearing loss in patients with
Hanneke I Vos1, Henk-Jan Guchelaar, Hans Gelderblom
1aLaboratory of Pediatric Oncology bDepartment of Pediatric Hematology and Oncology, Department of Pediatrics Departments of cHuman Genetics dMedical Oncology, Radboud university medical center, Nijmegen Departments of eClinical Pharmacy & Toxicology fMedical Oncology, Leiden University Medical Center, Leiden gDepartment of Pediatric Hematology and Oncology, University Medical Center Groningen, Groningen hDepartment of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
Objective:
Irreversible hearing loss is a frequent side effect of the chemotherapeutic agent cisplatin and shows considerable interpatient variability. The variant rs1872328 in the ACYP2 gene was recently identified as a risk factor for the development of cisplatin-induced ototoxicity in children with brain tumors. We aimed to replicate this finding in patients with osteosarcoma.
Methods:
An independent cohort of 156 patients was genotyped for the rs1872328 variant and evaluated for the presence of cisplatin-induced ototoxicity.
Results:
A significant association was observed between carriership of the A allele and cisplatin-induced ototoxicity after the end of treatment (P=0.027).
Conclusion:
This is the first study replicating the association of ACYP2 variant rs1872328 with cisplatin-induced ototoxicity in patients with osteosarcoma who did not receive potentially ototoxic cranial irradiation. Hence, the ACYP2 variant should be considered a predictive pharmacogenetic marker for hearing loss, which may be used to guide therapies for patients treated with cisplatin.
