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. 2014 Dec 31;9(12):e115869. doi: 10.1371/journal.pone.0115869. eCollection 2014.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antineoplastic Agents
  • Methyltransferases
  • COMT protein, human
  • Catechol O-Methyltransferase
  • thiopurine methyltransferase
  • Cisplatin

Grant support

This project was supported by a grant from the Foundation KiKa, Amstelveen, The Netherlands and the Asociación Española Contra el Cáncer, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.