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 Winther, Catherine 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, 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 Winther, Catherine 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
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.
Keywords: Adverse drug reaction; Cancer survivors; Childhood cancer; Cisplatin: carboplatin; Drug-induced ototoxicity; Genetic markers; Multicenter cohort study; Pharmacogenetics.
Conflict of interest statement
The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article.
© 2020 The Authors.
References
- Byrne J, Grabow D, Campbell H, O'Brien K, Bielack S, Am Zehnhoff-Dinnesen A. PanCareLIFE: The scientific basis for a European project to improve long-term care regarding fertility, ototoxicity and health-related quality of life after cancer occurring among children and adolescents. Eur. J. Cancer. 2018;103:227–237.
- Winther JF, Kenborg L, Byrne J, Hjorth L, Kaatsch P, Kremer LC. Childhood cancer survivor cohorts in Europe. Acta Oncol. 2015;54:655–668.
- Clemens E, Meijer AJ, Broer L, Langer T, van der Kooi AL, Uitterlinden AG. Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study. JMIR Res. Protoc. 2019;8:e11868.
- Schmidt CM, Bartholomaus E, Deuster D, Heinecke A, Dinnesen AG. The "Muenster classification" of high frequency hearing loss following cisplatin chemotherapy. Hno. 2007;55:299–306.
- Langer T, Clemens E, Broer L, Uitterlinden AG, de Vries A, van Grotel M. Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: results of the European PanCareLIFE cohort study. Eur J Cancer. 2020 In Press.
Source: PubMed