Replication of a genetic variant in ACYP2 associated with cisplatin-induced hearing loss in patients with osteosarcoma

Abstract

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.