TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial...

Full description

Saved in:

Bibliographic Details
Published in:	NPJ precision oncology Vol. 5; no. 1; pp. 64 - 8
Main Authors:	Meijer, A. J. M., Diepstraten, F. A., Langer, T., Broer, L., Domingo, I. K., Clemens, E., Uitterlinden, A. G., de Vries, A. C. H., van Grotel, M., Vermeij, W. P., Ozinga, R. A., Binder, H., Byrne, J., van Dulmen-den Broeder, E., Garrè, M. L., Grabow, D., Kaatsch, P., Kaiser, M., Kenborg, L., Winther, J. F., Rechnitzer, C., Hasle, H., Kepak, T., Kepakova, K., Tissing, W. J. E., van der Kooi, A. L. F., Kremer, L. C. M., Kruseova, J., Pluijm, S. M. F., Kuehni, C. E., van der Pal, H. J. H., Parfitt, R., Spix, C., Tillmanns, A., Deuster, D., Matulat, P., Calaminus, G., Hoetink, A. E., Elsner, S., Gebauer, J., Haupt, R., Lackner, H., Blattmann, C., Neggers, S. J. C. M. M., Rassekh, S. R., Wright, G. E. B., Brooks, B., Nagtegaal, A. P., Drögemöller, B. I., Ross, C. J. D., Bhavsar, A. P., am Zehnhoff-Dinnesen, A. G., Carleton, B. C., Zolk, O., van den Heuvel-Eibrink, M. M.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 14-07-2021 Nature Publishing Group Nature Portfolio
Subjects:	631/208/205/2138 692/699/67/2332 Brief Communication Cancer Cancer Research Chemotherapy Cytotoxicity Gene Therapy Genotype & phenotype Health risks Hearing loss Human Genetics Internal Medicine Medicine Medicine & Public Health Mutation Oncology Pediatrics Side effects
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts ( n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10 −10 , OR 3.11, 95% CI 2.2–4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.
ISSN:	2397-768X 2397-768X
DOI:	10.1038/s41698-021-00178-z