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Platinum-induced ototoxicity in pediatric cancer survivors: GSTP1 c.313A>G variant association

Laila M Sherief1, Elhamy Rifky1, Mohamed Attia2

  • 1Department of Pediatrics and Pediatric Hematology/Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Medicine
|November 18, 2022
PubMed

Insights

Platinum-based chemotherapy can cause hearing loss in childhood cancer survivors. The GSTP1 c.313A>G genetic variant is associated with an increased risk of this platinum-induced ototoxicity.

Area of Science:

  • Oncology
  • Genetics
  • Audiology

Background:

  • Platinum compounds, like cisplatin and carboplatin, are vital in pediatric cancer treatment.
  • Hearing damage (ototoxicity) is a significant toxic side effect of platinum-based chemotherapy, stemming from irreversible hair cell degeneration.
  • Genetic factors may influence susceptibility to platinum-induced ototoxicity.

Purpose of the Study:

  • To determine the frequency of ototoxicity in childhood cancer survivors treated with platinum agents.
  • To identify risk factors associated with platinum-induced ototoxicity.
  • To investigate the relationship between the GSTP1 c.313A>G (rs1695) polymorphism and ototoxicity in these survivors.

Main Methods:

  • A cross-sectional study involving 64 childhood cancer survivors who completed platinum-based chemotherapy at least two years prior.
  • Comprehensive audiological evaluations were performed to assess hearing loss.
  • Genotyping was conducted to identify the presence of GSTP1 c.313A>G polymorphisms (rs1695).

Main Results:

  • Hearing loss (HL) was identified in 25% of the survivors (16/64).
  • A significant association was found between the mutant GSTP1 rs1695 genotype and platinum-induced ototoxicity (P = .035).
  • Ototoxicity incidence varied by cancer type, with osteosarcoma patients showing the highest rate (28.1%).

Conclusions:

  • The GSTP1 c.313A>G variant may increase the risk of hearing loss in pediatric oncology patients receiving cisplatin or carboplatin chemotherapy.
  • Genetic predisposition, specifically the GSTP1 rs1695 polymorphism, is a crucial factor in platinum-induced ototoxicity.
  • Further research is warranted to explore genetic markers for predicting and mitigating ototoxicity in cancer survivors.

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