Analysis of genetic and non genetic risk factors for cisplatin ototoxicity in pediatric patients

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• 作者：Yü ; ksel Olgun^a ; ^{yuksel.olgun@deu.edu.tr" class="auth_mail" title="E-mail the corresponding author} ; Safiye Aktaş^b ; Zekiye Altun^b ; Gü ; nay Kırkım^c ; Deniz Ç ; akır Kızmazoğlu^d ; Ayşe Pınar Erç ; etin^b ; Banu Demir^c ; Dilek İnce^d ; Kamer Mutafoğlu^d ; Bengü ; Demirağ^e ; Hü ; lya Ellidokuz^f ; Nur Olgun^d ; Enis Alpin Gü ; neri^a
• 关键词：Cisplatin ; Ototoxicity ; Single nucleotide polymorphism
• 刊名：International Journal of Pediatric Otorhinolaryngology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：90
• 期：Complete
• 页码：64-69
• 全文大小：425 K

文摘

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.