title: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: aLaboratory 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.
authors.forename: Hanneke I
authors.initials: HI
authors.lastname: Vos
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Eveline S J M
authors.initials: ES
authors.lastname: de Bont
authors.forename: Leontien C M
authors.initials: LC
authors.lastname: Kremer
authors.forename: Anne Marlies
authors.initials: AM
authors.lastname: Naber
authors.forename: Marina H
authors.initials: MH
authors.lastname: Hakobjan
authors.forename: Winette T A
authors.initials: WT
authors.lastname: van der Graaf
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Coenen
authors.forename: Dunja Maroeska W M
authors.initials: DM
authors.lastname: te Loo
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002648:Child; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced* / Q000235:genetics; D006801:Humans; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; D000097024:Acylphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D000970:Antineoplastic Agents; D002945:Cisplatin; D000097024:Acylphosphatase; C000612927:ACYP2 protein, human