Replication of a genetic variant in ACYP2 associated with cisplatin-induced hearing loss in patients with osteosarcoma
SourcePharmacogenetics and Genomics, 26, 5, (2016), pp. 243-7
Article / Letter to editor
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Paediatrics - OUD tm 2017
Pharmacogenetics and Genomics
SubjectRadboudumc 5: Inflammatory diseases RIHS: Radboud Institute for Health Sciences; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health Sciences; Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life Sciences
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.
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