title: Genetic variation in Otos is associated with cisplatin-induced ototoxicity.
abstract: BACKGROUND
  Ototoxicity is an adverse drug reaction that may limit the effective use of cisplatin chemotherapy. Given the reported in vitro protective role of the gene Otos in response to cisplatin, this study aimed to explore the potential of Otos as a genetic modifier of ototoxicity.
  
  
  METHODS
  One hundred South African cisplatin-receiving cancer patients with baseline and follow-up audiometric data were screened for variation in exonic target regions of Otos using direct cycle sequencing.
  
  
  RESULTS
  A total of 29 genetic variants were identified. The G alleles of Otos rs77124181 (c.-192-182C>G) and rs2291767 (c.-192-22A>G) were over-represented in ototoxicity-free patients (p = 0.022). Cumulative cisplatin dose and anatomical site of cancer were also associated with ototoxicity, while self-reported ethnicity associated with the ototoxic severity.
  
  
  CONCLUSIONS
  This study indicates a potentially protective role for the variant G alleles of SNPs rs77124181 and rs2291767 in Otos against the development of cisplatin-induced ototoxicity.
authors.affiliation: MRC Human Genetics Research Unit, Division of Human Genetics, Institute of Infectious Diseases & Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Spracklen
authors.forename: Heather
authors.initials: H
authors.lastname: Whitehorn
authors.forename: Anna Alvera
authors.initials: AA
authors.lastname: Vorster
authors.forename: Lebogang
authors.initials: L
authors.lastname: Ramma
authors.forename: Sameera
authors.initials: S
authors.lastname: Dalvie
authors.forename: Rajkumar S
authors.initials: RS
authors.lastname: Ramesar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D005260:Female; D014644:Genetic Variation; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C503045:OTOS protein, human; D011506:Proteins; D002945:Cisplatin
keywords: Otos; South Africa; cisplatin; hearing loss; ototoxicity