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

Melanie M Hagleitner, Marieke J H Coenen, Ana Patino-Garcia, Eveline S J M de Bont, Anna Gonzalez-Neira, Hanneke I Vos, Frank N van Leeuwen, Hans Gelderblom, Peter M Hoogerbrugge, Henk-Jan Guchelaar, Maroeska W M Te Loo

Research output: Contribution to journalArticlepeer-review

Abstract

Treatment with cisplatin-containing chemotherapy regimens causes hearing loss in 40-60% of cancer patients. It has been suggested that genetic variants in the genes encoding thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) can predict the development of cisplatin-induced ototoxicity and may explain interindividual variability in sensitivity to cisplatin-induced hearing loss. Two recently published studies however, sought to validate these findings and showed inconsistent results. The aim of this study was to evaluate the role of polymorphisms in the TPMT and COMT genes in cisplatin-induced ototoxicity. Therefore we investigated two independent cohorts of 110 Dutch and 38 Spanish patients with osteosarcoma and performed a meta-analysis including all previously published studies resulting in a total population of 664 patients with cancer. With this largest meta-analysis performed to date, we show that the influence of TPMT and COMT on the development of cisplatin-induced hearing loss may be less important than previously suggested.

Original languageEnglish
Pages (from-to)e115869
JournalPloS one
Volume9
Issue number12
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Adolescent
  • Adult
  • Antineoplastic Agents/adverse effects
  • Bone Neoplasms/drug therapy
  • Catechol O-Methyltransferase/genetics
  • Child
  • Child, Preschool
  • Cisplatin/adverse effects
  • Female
  • Genotype
  • Hearing Loss/chemically induced
  • Humans
  • Male
  • Methyltransferases/genetics
  • Netherlands
  • Osteosarcoma/drug therapy
  • Polymorphism, Single Nucleotide
  • Spain
  • Young Adult

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