TY - JOUR
T1 - TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
AU - PanCareLIFE Consortium
AU - Meijer, A. J.M.
AU - Diepstraten, F. A.
AU - Langer, T.
AU - Broer, L.
AU - Domingo, I. K.
AU - Clemens, E.
AU - Uitterlinden, A. G.
AU - de Vries, A. C.H.
AU - van Grotel, M.
AU - Vermeij, W. P.
AU - Ozinga, R. A.
AU - Binder, H.
AU - Byrne, J.
AU - van Dulmen-den Broeder, E.
AU - Garrè, M. L.
AU - Grabow, D.
AU - Kaatsch, P.
AU - Kaiser, M.
AU - Kenborg, L.
AU - Winther, J. F.
AU - Rechnitzer, C.
AU - Hasle, H.
AU - Kepak, T.
AU - Kepakova, K.
AU - Tissing, W. J.E.
AU - van der Kooi, A. L.F.
AU - Kremer, L. C.M.
AU - Kruseova, J.
AU - Pluijm, S. M.F.
AU - Kuehni, C. E.
AU - van der Pal, H. J.H.
AU - Parfitt, R.
AU - Spix, C.
AU - Tillmanns, A.
AU - Deuster, D.
AU - Matulat, P.
AU - Calaminus, G.
AU - Hoetink, A. E.
AU - Elsner, S.
AU - Gebauer, J.
AU - Haupt, R.
AU - Lackner, H.
AU - Blattmann, C.
AU - Neggers, S. J.C.M.M.
AU - Rassekh, S. R.
AU - Wright, G. E.B.
AU - van den Heuvel-Eibrink, M. M.
AU - van der Kooi, A. L.F.
AU - Kremer, L. C.M.
AU - van der Pal, H. J.H.
N1 - © 2021. The Author(s).
PY - 2021/6/14
Y1 - 2021/6/14
N2 - 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.
AB - 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.
UR - https://www.mendeley.com/catalogue/012093c6-1493-3f26-a929-8d7c020d5f7a/
U2 - 10.1038/s41698-021-00178-z
DO - 10.1038/s41698-021-00178-z
M3 - Article
C2 - 34262104
SN - 2397-768X
VL - 5
SP - 64
JO - NPJ precision oncology
JF - NPJ precision oncology
IS - 1
M1 - 64
ER -