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

A J M Meijer; F A Diepstraten; T Langer; L Broer; I K Domingo; E Clemens; A G Uitterlinden; A C H de Vries; M van Grotel; W P Vermeij; R A Ozinga; H Binder; J Byrne; E van Dulmen-den Broeder; M L Garrè; D Grabow; P Kaatsch; M Kaiser; L Kenborg; J F Winther; C Rechnitzer; H Hasle; T Kepak; K Kepakova; W J E Tissing; A L F van der Kooi; L C M Kremer; J Kruseova; S M F Pluijm; C E Kuehni; H J H van der Pal; R Parfitt; C Spix; A Tillmanns; D Deuster; P Matulat; G Calaminus; A E Hoetink; S Elsner; J Gebauer; R Haupt; H Lackner; C Blattmann; S J C M M Neggers; S R Rassekh; G E B Wright; B Brooks; A P Nagtegaal; B I Drögemöller; C J D Ross; PanCareLIFE consortium

doi:10.1038/s41698-021-00178-z

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

A J M Meijer, F A Diepstraten, T Langer, L Broer, I K Domingo, E Clemens, A G Uitterlinden, A C H de Vries, M van Grotel, W P Vermeij, R A Ozinga, H Binder, J Byrne, E van Dulmen-den Broeder, M L Garrè, D Grabow, P Kaatsch, M Kaiser, L Kenborg, J F WintherC Rechnitzer, H Hasle, T Kepak, K Kepakova, W J E Tissing, A L F van der Kooi, L C M Kremer, J Kruseova, S M F Pluijm, C E Kuehni, H J H van der Pal, R Parfitt, C Spix, A Tillmanns, D Deuster, P Matulat, G Calaminus, A E Hoetink, S Elsner, J Gebauer, R Haupt, H Lackner, C Blattmann, S J C M M Neggers, S R Rassekh, G E B Wright, B Brooks, A P Nagtegaal, B I Drögemöller, C J D Ross, PanCareLIFE consortium

Department of Paediatrics and Adolescent Medicine

Abstract

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.

Original language	English
Article number	64
Journal	NPJ precision oncology
Volume	5
Issue number	1
Pages (from-to)	64
ISSN	2397-768X
DOIs	https://doi.org/10.1038/s41698-021-00178-z
Publication status	Published - 14 Jul 2021

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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., ... PanCareLIFE consortium (2021). TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study. NPJ precision oncology, 5(1), 64. Article 64. https://doi.org/10.1038/s41698-021-00178-z

Meijer, AJM, Diepstraten, FA, Langer, T, Broer, L, Domingo, IK, Clemens, E, Uitterlinden, AG, de Vries, ACH, van Grotel, M, Vermeij, WP, Ozinga, RA, Binder, H, Byrne, J, van Dulmen-den Broeder, E, Garrè, ML, Grabow, D, Kaatsch, P, Kaiser, M, Kenborg, L, Winther, JF, Rechnitzer, C, Hasle, H, Kepak, T, Kepakova, K, Tissing, WJE, van der Kooi, ALF, Kremer, LCM, Kruseova, J, Pluijm, SMF, Kuehni, CE, van der Pal, HJH, Parfitt, R, Spix, C, Tillmanns, A, Deuster, D, Matulat, P, Calaminus, G, Hoetink, AE, Elsner, S, Gebauer, J, Haupt, R, Lackner, H, Blattmann, C, Neggers, SJCMM, Rassekh, SR, Wright, GEB, Brooks, B, Nagtegaal, AP, Drögemöller, BI, Ross, CJD & PanCareLIFE consortium 2021, 'TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study', NPJ precision oncology, vol. 5, no. 1, 64, pp. 64. https://doi.org/10.1038/s41698-021-00178-z

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

abstract = "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.",

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doi = "10.1038/s41698-021-00178-z",

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TY - JOUR

T1 - TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

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 - Brooks, B

AU - Nagtegaal, A P

AU - Drögemöller, B I

AU - Ross, C J D

AU - PanCareLIFE consortium

PY - 2021/7/14

Y1 - 2021/7/14

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 - http://www.scopus.com/inward/record.url?scp=85117051914&partnerID=8YFLogxK

U2 - 10.1038/s41698-021-00178-z

DO - 10.1038/s41698-021-00178-z

M3 - Journal article

C2 - 34262104

SN - 2397-768X

VL - 5

SP - 64

JO - NPJ precision oncology

JF - NPJ precision oncology

IS - 1

M1 - 64

ER -

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

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