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Systematic Review and Meta-Analysis of the Influence of Genetic Variation on Ototoxicity in Platinum-Based

Daniel Z Hong1, Thaned C C Ong1, Dhayan P Timbadia1

  • 1Department of Otolaryngology-Head and Neck Surgery, National University of Singapore, Singapore, Singapore.

Otolaryngology--Head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery
|February 21, 2023
PubMed
Abstract

Insights

Genetic variations impact platinum-based chemotherapy-induced ototoxicity. Certain gene alleles offer protection, while others increase risk, enabling personalized cancer care strategies.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Toxicology

Background:

  • Platinum-based chemotherapy (PBC) is a cornerstone in cancer treatment but can cause ototoxicity, a significant side effect impacting patient quality of life.
  • Genetic factors are increasingly recognized as modulators of drug response and toxicity, necessitating investigation into their role in PBC-induced ototoxicity.

Approach:

  • A comprehensive meta-analysis was conducted, systematically searching major databases (PubMed, Embase, Cochrane, Web of Science) up to May 2022.
  • Data from 32 articles, encompassing 4406 participants, were analyzed to identify associations between genetic polymorphisms and ototoxicity.
  • Odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects models to determine effect sizes.

Key Points:

  • The A allele in ACYP2 rs1872328 was significantly associated with increased ototoxicity risk (OR: 2.61).
  • Specific alleles (COMT rs4646316, COMT rs9332377) showed associations with ototoxicity when considering cisplatin use only.
  • The CT/TT genotype in ERCC2 rs1799793 demonstrated an otoprotective effect (OR: 0.50).
  • Several polymorphisms (COMT rs4646316, GSTP1 rs1965, XPC rs2228001) showed significant effects when excluding carboplatin or radiotherapy.

Conclusions:

  • This meta-analysis identifies specific genetic polymorphisms that confer either ototoxic or otoprotective effects in patients receiving platinum-based chemotherapy.
  • The global prevalence of some identified alleles suggests potential for widespread application of polygenic screening.
  • These findings support the development of personalized medicine approaches for evaluating cumulative genetic risk and optimizing cancer treatment strategies to mitigate ototoxicity.
Keywords:
geneticsototoxicityplatinum chemotherapysingle-nucleotide polymorphism

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