Cisplatin ototoxicity in children: risk factors and its relationship with polymorphisms of DNA repair genes ERCC1, ERCC2, and XRCC1
- 135 Downloads
We aimed to investigate the cisplatin-related hearing toxicity and its possible relationship with polymorphic variants in DNA repair genes, ERCC1, ERCC2, and XRCC1.
Fifty patients treated with cisplatin in the past were included in the study. There were 29 females and 21 males; mean age 13.4 ± 6.0 years). The polymorphism in DNA repair genes was studied using primer and probes in Light Cycler device after DNA isolation was carried out with PCR technique. The polymorphisms and clinical risk factors were evaluated using Chi square test and logistic regression modelling.
The patients had hearing loss in 44%. For ERCC1 gene, the patients with hearing loss had 50% of GG (wild type), 40.9% of AG and 9.1% of AA genotypes, while the patients without hearing loss had 28.6% of GG, 53.5% of AG, and 17.9% of AA genotypes. For ERCC2 gene, the patients with hearing loss had 18.2% of GG (wild type), 40.9% of TG, and 40.9% of TT genotypes, while the patients without hearing loss had 10.7% of GG 39.3% of TG, and 50% of TT genotypes. For XRCC1 gene, the patients with hearing loss had 18.2% of CC (wild type), 59.1% of CT, and 22.7% of TT genotypes, while the patients without hearing loss had 35.7% of CC, 50% of CT, and 14.3% of TT genotypes. There was no statistically significant association among the groups (p = 0.24).
We did not find a relationship between DNA repair gene polymorphisms and hearing toxicity of cisplatin.
KeywordsOtotoxicity Cisplatin DNA repair genes Polymorphism Children
Compliance with ethical standards
Conflict of interest
The author(s) declare that they have no competing interests.
- 1.Brock PR, Knight KR, Freyer DR, Campbell KC, Steyger PS, Blakley BW et al (2012) Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition, and protection, including a new international society of pediatric oncology boston ototoxicity scale. J Clin Oncol 30(19):2408–2417. https://doi.org/10.1200/JCO.2011.39.1110 CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Wheeler HE, Gamazon ER, Frisina RD, Perez-Cervantes C, El Charif O, Mapes B et al (2017) Variants in WFS1 and other mendelian deafness genes are associated with cisplatin-associated ototoxicity. Clin Cancer Res 23(13):3325–3333. https://doi.org/10.1158/1078-0432.CCR-16-2809 CrossRefPubMedGoogle Scholar
- 13.Soliman SE, D’Silva CN, Dimaras H, Dzneladze I, Chan H, Gallie BL (2018) Clinical and genetic associations for carboplatin-related ototoxicity in children treated for retinoblastoma: A retrospective noncomparative single-institute experience. Pediatr Blood Cancer 65(5):26931 10.1002/pbc.26931 CrossRefGoogle Scholar
- 14.Choeyprasert W, Sawangpanich R, Lertsukprasert K, Udomsubpayakul U, Songdej D, Unurathapan U et al (2013) Cisplatin-induced ototoxicity in pediatric solid tumors: the role of glutathione S-transferases and megalin genetic polymorphisms. J Pediatr Hematol Oncol 35(4):e138–e143. https://doi.org/10.1097/MPH.0b013e3182707fc5 CrossRefPubMedGoogle Scholar
- 20.Hagleitner MM, Coenen MJ, Patino-Garcia A, de Bont ES, Gonzalez-Neira A, Vos HI et al (2014) Influence of genetic variants in TPMT and COMT associated with cisplatin induced hearing loss in patients with cancer: two new cohorts and a meta-analysis reveal significant heterogeneity between cohorts. PLoS One 9(12):e115869. https://doi.org/10.1371/journal.pone.0115869 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Mironovich OL, Bliznetz EA, Garbaruk ES, Belogurova MB, Subora NV, Varfolomeeva SR et al (2018) The analysis of the association of the polymorphic variants of the TPMT, COMT, and ABCC3 genes with the development of hearing disorders induced by the cisplatin treatment. Vestn Otorinolaringol 83(4):60–66. https://doi.org/10.17116/otorino201883460 CrossRefPubMedGoogle Scholar
- 23.Zhou W, Gurubhagavatula S, Liu G, Park S, Neuberg DS, Wain JC et al (2004) Excision repair cross-complementation group 1 polymorphism predicts overall survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. Clin Cancer Res 10:4939–4943CrossRefGoogle Scholar