title: Analysis of genetic and non genetic risk factors for cisplatin ototoxicity in pediatric patients.
abstract: OBJECTIVE
  The aim of this study was to analyse the genetic and non genetic risk factors for cisplatin ototoxicity.
  
  
  METHODS
  This study was conducted on 72 children who received cisplatin based chemotherapy. Brock and Muenster classifications were used to evaluate ototoxicity seen in these children. 6 single nucleotide polymorphisms (SNP); ERCC1 rs 11615, GSTP1 rs1138272, GSTP1 rs1695, LRP2 rs 2075252, TPMT rs 12201199, COMT rs 9332377, were evaluated as genetic factors by real time PCR. Non genetic factors such as cranial irradiation, cumulative doses of cisplatin, age, gender, administration of other ototoxic drugs were analysed as well. By using Chi-square test, risk factors were matched with the ototoxicity classifications. Significant risk factors were reevaluated using logistic regression modelling.
  
  
  RESULTS
  According to univariate analyses, male gender, co-treatment with aminoglycosides and mutant genotype of GSTP1 rs1695 were significantly related with cisplatin ototoxicity. Logistic regression modelling analyses also showed that male gender, co-treatment with aminoglycosides were found to be significantly related with cisplatin ototoxicity. Mutant genotype of GSTP1 rs1695 was not found to be significant, but close to the level of statistical significance.
  
  
  CONCLUSIONS
  Male gender, co-treatment with aminoglycosides are significant risk factors for cisplatin ototoxicity in pediatric patients. Mutant genotype of GSTP1 rs1695 seems to be a genetic risk factor in univariate analyses, although not confirmed by multivariate analyses. Therefore, GSTP1 rs1695 SNP needs to be studied in larger series.
authors.affiliation: Dokuz Eylül University School of Medicine, Department of Otorhinolaryngology, Izmir, Turkey. Electronic address: yuksel.olgun@deu.edu.tr.
authors.forename: Yüksel
authors.initials: Y
authors.lastname: Olgun
authors.affiliation: Dokuz Eylül University Institute of Oncology, Department of Basic Oncology, Izmir, Turkey.
authors.forename: Safiye
authors.initials: S
authors.lastname: Aktaş
authors.affiliation: Dokuz Eylül University Institute of Oncology, Department of Basic Oncology, Izmir, Turkey.
authors.forename: Zekiye
authors.initials: Z
authors.lastname: Altun
authors.affiliation: Dokuz Eylul University School of Medicine Department of Otorhinolaryngology, Unit of Hearing Speech and Balance, Izmir, Turkey.
authors.forename: Günay
authors.initials: G
authors.lastname: Kırkım
authors.affiliation: Dokuz Eylül University School of Medicine, Department of Pediatric Oncology, Izmir, Turkey.
authors.forename: Deniz Çakır
authors.initials: DÇ
authors.lastname: Kızmazoğlu
authors.affiliation: Dokuz Eylül University Institute of Oncology, Department of Basic Oncology, Izmir, Turkey.
authors.forename: Ayşe Pınar
authors.initials: AP
authors.lastname: Erçetin
authors.affiliation: Dokuz Eylul University School of Medicine Department of Otorhinolaryngology, Unit of Hearing Speech and Balance, Izmir, Turkey.
authors.forename: Banu
authors.initials: B
authors.lastname: Demir
authors.affiliation: Dokuz Eylül University School of Medicine, Department of Pediatric Oncology, Izmir, Turkey.
authors.forename: Dilek
authors.initials: D
authors.lastname: İnce
authors.affiliation: Dokuz Eylül University School of Medicine, Department of Pediatric Oncology, Izmir, Turkey.
authors.forename: Kamer
authors.initials: K
authors.lastname: Mutafoğlu
authors.affiliation: Dr Behçet Uz Children's Hospital, Department of Pediatric Oncology, Izmir, Turkey.
authors.forename: Bengü
authors.initials: B
authors.lastname: Demirağ
authors.affiliation: Dokuz Eylül University School of Medicine, Department of Biostatistics, Izmir, Turkey.
authors.forename: Hülya
authors.initials: H
authors.lastname: Ellidokuz
authors.affiliation: Dokuz Eylül University School of Medicine, Department of Pediatric Oncology, Izmir, Turkey.
authors.forename: Nur
authors.initials: N
authors.lastname: Olgun
authors.affiliation: Dokuz Eylül University School of Medicine, Department of Otorhinolaryngology, Izmir, Turkey.
authors.forename: Enis Alpin
authors.initials: EA
authors.lastname: Güneri
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000617:Aminoglycosides / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004427:Ear Diseases / Q000139:chemically induced* / Q000235:genetics*; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D000617:Aminoglycosides; D000970:Antineoplastic Agents; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D002945:Cisplatin
keywords: Cisplatin; Ototoxicity; Single nucleotide polymorphism