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
SourcePLoS One, 9, 12, (2014), article e115869
Article / Letter to editor
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Paediatrics - OUD tm 2017
SubjectRadboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 5: Inflammatory diseases RIHS: Radboud Institute for Health Sciences; Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life Sciences
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.
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