Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset

Thorsten Langer, Eva Clemens, Linda Broer, Lara Maier, André G. Uitterlinden, Andrica C.H. de Vries, Martine van Grotel, Saskia F.M. Pluijm, Harald Binder, Benjamin Mayer, Annika von dem Knesebeck, Julianne Byrne, Eline van Dulmen-den Broeder, Marco Crocco, Desiree Grabow, Peter Kaatsch, Melanie Kaiser, Claudia Spix, Line Kenborg, Jeanette F. WintherCatherine Rechnitzer, Henrik Hasle, Tomas Kepak, Anne Lotte F. van der Kooi, Leontien C. Kremer, Jarmila Kruseova, Stefan Bielack, Benjamin Sorg, Stefanie Hecker-Nolting, Claudia E. Kuehni, Marc Ansari, Martin Kompis, Heleen J. van der Pal, Ross Parfitt, Dirk Deuster, Peter Matulat, Amelie Tillmanns, Wim J.E. Tissing, Jörn D. Beck, Susanne Elsner, Antoinette am Zehnhoff-Dinnesen, Marry M. van den Heuvel-Eibrink, Oliver Zolk*, PanCareLIFE Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2) were genotyped. The genotype and phenotype data represent a resource for conducting meta-analyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment.

Original languageEnglish
Article number106227
JournalData in Brief
Volume32
DOIs
Publication statusPublished - Oct 2020

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