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

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

PanCareLIFE Consortium

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
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 - 14.07.2021

Research Areas and Centers

Research Area: Center for Population Medicine and Public Health (ZBV)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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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.",

author = "{PanCareLIFE Consortium} and Meijer, {A J M} and Diepstraten, {F A} and T Langer and L Broer and Domingo, {I K} and E Clemens and Uitterlinden, {A G} and {de Vries}, {A C H} and {van Grotel}, M and Vermeij, {W P} and Ozinga, {R A} and H Binder and J Byrne and {van Dulmen-den Broeder}, E and Garr{\`e}, {M L} and D Grabow and P Kaatsch and M Kaiser and L Kenborg and Winther, {J F} and C Rechnitzer and H Hasle and T Kepak and K Kepakova and Tissing, {W J E} and {van der Kooi}, {A L F} and Kremer, {L C M} and J Kruseova and Pluijm, {S M F} and Kuehni, {C E} and {van der Pal}, {H J H} and R Parfitt and C Spix and A Tillmanns and D Deuster and P Matulat and G Calaminus and Hoetink, {A E} and S Elsner and J Gebauer and R Haupt and H Lackner and C Blattmann and Neggers, {S J C M M} and Rassekh, {S R} and Wright, {G E B} and B Brooks and Nagtegaal, {A P} and Dr{\"o}gem{\"o}ller, {B I} and Ross, {C J D}",

note = "{\textcopyright} 2021. The Author(s).",

year = "2021",

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

language = "English",

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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 - Brooks, B

AU - Nagtegaal, A P

AU - Drögemöller, B I

AU - Ross, C J D

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.

U2 - 10.1038/s41698-021-00178-z

DO - 10.1038/s41698-021-00178-z

M3 - Journal articles

C2 - 34262104

SN - 2397-768X

VL - 5

SP - 64

JO - NPJ precision oncology

JF - NPJ precision oncology

IS - 1

ER -

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

Abstract

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