Yüksel Olgun1, Safiye Aktaş2, Zekiye Altun2, Günay Kırkım3, Deniz Çakır Kızmazoğlu4, Ayşe Pınar Erçetin2, Banu Demir3, Dilek İnce4, Kamer Mutafoğlu4, Bengü Demirağ5, Hülya Ellidokuz6, Nur Olgun4, Enis Alpin Güneri7. 1. Dokuz Eylül University School of Medicine, Department of Otorhinolaryngology, Izmir, Turkey. Electronic address: yuksel.olgun@deu.edu.tr. 2. Dokuz Eylül University Institute of Oncology, Department of Basic Oncology, Izmir, Turkey. 3. Dokuz Eylul University School of Medicine Department of Otorhinolaryngology, Unit of Hearing Speech and Balance, Izmir, Turkey. 4. Dokuz Eylül University School of Medicine, Department of Pediatric Oncology, Izmir, Turkey. 5. Dr Behçet Uz Children's Hospital, Department of Pediatric Oncology, Izmir, Turkey. 6. Dokuz Eylül University School of Medicine, Department of Biostatistics, Izmir, Turkey. 7. Dokuz Eylül University School of Medicine, Department of Otorhinolaryngology, Izmir, Turkey.
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. CONCLUSION: 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.
OBJECTIVE: The aim of this study was to analyse the genetic and non genetic risk factors for cisplatinototoxicity. 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, GSTP1rs1138272, GSTP1rs1695, LRP2rs 2075252, TPMTrs 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 GSTP1rs1695 were significantly related with cisplatinototoxicity. Logistic regression modelling analyses also showed that male gender, co-treatment with aminoglycosides were found to be significantly related with cisplatinototoxicity. Mutant genotype of GSTP1rs1695 was not found to be significant, but close to the level of statistical significance. CONCLUSION: Male gender, co-treatment with aminoglycosides are significant risk factors for cisplatinototoxicity in pediatric patients. Mutant genotype of GSTP1rs1695 seems to be a genetic risk factor in univariate analyses, although not confirmed by multivariate analyses. Therefore, GSTP1rs1695 SNP needs to be studied in larger series.
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