Cisplatin ototoxicity in children: risk factors and its relationship with polymorphisms of DNA repair genes ERCC1, ERCC2, and XRCC1

Cancer Chemother Pharmacol. 2019 Dec;84(6):1333-1338. doi: 10.1007/s00280-019-03968-2. Epub 2019 Oct 4.

Abstract

Purpose: We aimed to investigate the cisplatin-related hearing toxicity and its possible relationship with polymorphic variants in DNA repair genes, ERCC1, ERCC2, and XRCC1.

Methods: 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.

Results: 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).

Conclusion: We did not find a relationship between DNA repair gene polymorphisms and hearing toxicity of cisplatin.

Keywords: Children; Cisplatin; DNA repair genes; Ototoxicity; Polymorphism.

MeSH terms

  • Adolescent
  • Antineoplastic Agents / adverse effects*
  • Cancer Survivors / statistics & numerical data
  • Child
  • Cisplatin / adverse effects*
  • DNA Repair
  • DNA-Binding Proteins / genetics
  • Endonucleases / genetics
  • Female
  • Hearing Loss / chemically induced*
  • Hearing Loss / epidemiology
  • Hearing Loss / genetics
  • Humans
  • Male
  • Neoplasms / drug therapy*
  • Ototoxicity / epidemiology
  • Ototoxicity / etiology
  • Ototoxicity / genetics*
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Risk Factors
  • X-ray Repair Cross Complementing Protein 1 / genetics
  • Xeroderma Pigmentosum Group D Protein / genetics
  • Young Adult

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • ERCC1 protein, human
  • Endonucleases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Cisplatin