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...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/1a21ee1f4f0440f184693f4b2b482abf |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:1a21ee1f4f0440f184693f4b2b482abf |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:1a21ee1f4f0440f184693f4b2b482abf2021-12-02T16:14:15ZTCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study10.1038/s41698-021-00178-z2397-768Xhttps://doaj.org/article/1a21ee1f4f0440f184693f4b2b482abf2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00178-zhttps://doaj.org/toc/2397-768XAbstract 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.A. J. M. MeijerF. A. DiepstratenT. LangerL. BroerI. K. DomingoE. ClemensA. G. UitterlindenA. C. H. de VriesM. van GrotelW. P. VermeijR. A. OzingaH. BinderJ. ByrneE. van Dulmen-den BroederM. L. GarrèD. GrabowP. KaatschM. KaiserL. KenborgJ. F. WintherC. RechnitzerH. HasleT. KepakK. KepakovaW. J. E. TissingA. L. F. van der KooiL. C. M. KremerJ. KruseovaS. M. F. PluijmC. E. KuehniH. J. H. van der PalR. ParfittC. SpixA. TillmannsD. DeusterP. MatulatG. CalaminusA. E. HoetinkS. ElsnerJ. GebauerR. HauptH. LacknerC. BlattmannS. J. C. M. M. NeggersS. R. RassekhG. E. B. WrightB. BrooksA. P. NagtegaalB. I. DrögemöllerC. J. D. RossA. P. BhavsarA. G. am Zehnhoff-DinnesenB. C. CarletonO. ZolkM. M. van den Heuvel-Eibrinkthe PanCareLIFE Consortiumand the CPNDS ConsortiumNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-8 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 A. P. Bhavsar A. G. am Zehnhoff-Dinnesen B. C. Carleton O. Zolk M. M. van den Heuvel-Eibrink the PanCareLIFE Consortium and the CPNDS Consortium TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study |
| description |
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. |
| format |
article |
| author |
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 A. P. Bhavsar A. G. am Zehnhoff-Dinnesen B. C. Carleton O. Zolk M. M. van den Heuvel-Eibrink the PanCareLIFE Consortium and the CPNDS Consortium |
| author_facet |
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 A. P. Bhavsar A. G. am Zehnhoff-Dinnesen B. C. Carleton O. Zolk M. M. van den Heuvel-Eibrink the PanCareLIFE Consortium and the CPNDS Consortium |
| author_sort |
A. J. M. Meijer |
| title |
TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study |
| title_short |
TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study |
| title_full |
TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study |
| title_fullStr |
TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study |
| title_full_unstemmed |
TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study |
| title_sort |
tcerg1l allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a pancarelife study |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/1a21ee1f4f0440f184693f4b2b482abf |
| work_keys_str_mv |
AT ajmmeijer tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT fadiepstraten tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT tlanger tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT lbroer tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT ikdomingo tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT eclemens tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT aguitterlinden tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT achdevries tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT mvangrotel tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT wpvermeij tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT raozinga tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT hbinder tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT jbyrne tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT evandulmendenbroeder tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT mlgarre tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT dgrabow tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT pkaatsch tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT mkaiser tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT lkenborg tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT jfwinther tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT crechnitzer tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT hhasle tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT tkepak tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT kkepakova tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT wjetissing tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT alfvanderkooi tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT lcmkremer tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT jkruseova tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT smfpluijm tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT cekuehni tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT hjhvanderpal tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT rparfitt tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT cspix tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT atillmanns tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT ddeuster tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT pmatulat tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT gcalaminus tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT aehoetink tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT selsner tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT jgebauer tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT rhaupt tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT hlackner tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT cblattmann tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT sjcmmneggers tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT srrassekh tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT gebwright tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT bbrooks tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT apnagtegaal tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT bidrogemoller tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT cjdross tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT apbhavsar tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT agamzehnhoffdinnesen tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT bccarleton tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT ozolk tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT mmvandenheuveleibrink tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT thepancarelifeconsortium tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy AT andthecpndsconsortium tcerg1lallelicvariationisassociatedwithcisplatininducedhearinglossinchildhoodcancerapancarelifestudy |
| _version_ |
1718384337115676672 |