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

Pharmacogenet Genomics. 2016 May;26(5):243-7. doi: 10.1097/FPC.0000000000000212.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases / genetics*
  • Adolescent
  • Adult
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Child
  • Cisplatin / adverse effects*
  • Cisplatin / therapeutic use
  • Female
  • Hearing Loss / chemically induced*
  • Hearing Loss / genetics
  • Humans
  • Male
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Polymorphism, Single Nucleotide*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Acid Anhydride Hydrolases
  • ACYP2 protein, human
  • acylphosphatase
  • Cisplatin