Genetic Determinants of Ototoxicity During and After Childhood
Cancer Treatment: Protocol for the PanCareLIFE Study

J 2019

Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study

CLEMENS, Eva, Annelot J. M. MEIJER, Linda BROER, Thorsten LANGER, Anne-Lode L. F. VAN DER KOOI et. al.

Basic information

Original name

Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study

Authors

CLEMENS, Eva (528 Netherlands, guarantor), Annelot J. M. MEIJER (528 Netherlands), Linda BROER (528 Netherlands), Thorsten LANGER (276 Germany), Anne-Lode L. F. VAN DER KOOI (528 Netherlands), Andre G. UITTERLINDEN (528 Netherlands), Andrica DE VRIES (528 Netherlands), Claudia E. KUEHNI (756 Switzerland), Maria L. GARRE (380 Italy), Tomáš KEPÁK (203 Czech Republic, belonging to the institution), Jarmila KRUSEOVA (203 Czech Republic), Jeanette F. WINTHER (208 Denmark), Leontien C. KREMER (528 Netherlands), Eline VAN DULMEN-DEN BROEDER (528 Netherlands), Wim J. E. TISSING (528 Netherlands), Catherine RECHNITZER (208 Denmark), Line KENBORG (208 Denmark), Henrik HASLE (208 Denmark), Desiree GRABOW (276 Germany), Ross PARFITT (276 Germany), Harald BINDER (276 Germany), Bruce C. CARLETON (124 Canada), Julianne BYRNE (372 Ireland), Peter KAATSCH (276 Germany), Antoinette Am ZEHNHOFF-DINNESEN (276 Germany), Oliver ZOLK (276 Germany) and Marry M. VAN DEN HEUVEL-EIBRINK (528 Netherlands)

Edition

JMIR RESEARCH PROTOCOLS, TORONTO, JMIR PUBLICATIONS, INC, 2019, 1929-0748

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Canada

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

RIV identification code

RIV/00216224:14110/19:00112793

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.2196/11868

UT WoS

000462890300033

Keywords in English

ototoxicity; hearing loss; childhood cancer survivors; cisplatin; genetics; GWAS; candidate genes; polymorphisms

Abstract

V originále

Background: Survival rates after childhood cancer now reach nearly 80% in developed countries. However, treatments that lead to survival and cure can cause serious adverse effects with lifelong negative impacts on survivor quality of life. Hearing impairment is a common adverse effect in children treated with cisplatin-based chemotherapy or cranial radiotherapy. Ototoxicity can extend from high-tone hearing impairment to involvement of speech frequencies. Hearing impairment can impede speech and language and neurocognitive development. Although treatment-related risk factors for hearing loss following childhood cancer treatment have been identified, the individual variability in toxicity of adverse effects after similar treatment between childhood cancer patients suggests a role for genetic susceptibility. Currently, 12 candidate gene approach studies have been performed to identify polymorphisms predisposing to platinum-induced ototoxicity in children being treated for cancer. However, results were inconsistent and most studies were underpowered and/or lacked replication. Objective: We describe the design of the PanCareLIFE consortium's work packages that address the genetic susceptibility of platinum-induced ototoxicity. Methods: As a part of the PanCareLIFE study within the framework of the PanCare consortium, we addressed genetic susceptibility of treatment-induced ototoxicity during and after childhood cancer treatment in a large European cohort by a candidate gene approach and a genome-wide association screening. Results: This study included 1124 survivors treated with cisplatin, carboplatin, or cranial radiotherapy for childhood cancer, resulting in the largest clinical European cohort assembled for this late effect to date. Within this large cohort we defined a group of 598 cisplatin-treated childhood cancer patients not confounded by cranial radiotherapy. The PanCareLIFE initiative provided, for the first time, a unique opportunity to confirm already identified determinants for hearing impairment during childhood cancer using a candidate gene approach and set up the first international genome-wide association study of cisplatin-induced direct ototoxicity in childhood cancer patients to identify novel allelic variants. Results will be validated in an independent replication cohort. Patient recruitment started in January 2015 and final inclusion was October 2017. We are currently performing the analyses and the first results are expected by the end of 2019 or the beginning of 2020. Conclusions: Genetic factors identified as part of this pan-European project, PanCareLIFE, may contribute to future risk prediction models that can be incorporated in future clinical trials of platinum-based therapies for cancer and may help with the development of prevention strategies.

Citovat

CLEMENS, Eva, Annelot J. M. MEIJER, Linda BROER, Thorsten LANGER, Anne-Lode L. F. VAN DER KOOI, Andre G. UITTERLINDEN, Andrica DE VRIES, Claudia E. KUEHNI, Maria L. GARRE, Tomáš KEPÁK, Jarmila KRUSEOVA, Jeanette F. WINTHER, Leontien C. KREMER, Eline VAN DULMEN-DEN BROEDER, Wim J. E. TISSING, Catherine RECHNITZER, Line KENBORG, Henrik HASLE, Desiree GRABOW, Ross PARFITT, Harald BINDER, Bruce C. CARLETON, Julianne BYRNE, Peter KAATSCH, Antoinette Am ZEHNHOFF-DINNESEN, Oliver ZOLK and Marry M. VAN DEN HEUVEL-EIBRINK. Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study. JMIR RESEARCH PROTOCOLS. TORONTO: JMIR PUBLICATIONS, INC, 2019, vol. 8, No 3, p. 1-11. ISSN 1929-0748. Available from: https://dx.doi.org/10.2196/11868.

@article{1612356,
   author = {Clemens, Eva and Meijer, Annelot J. M. and Broer, Linda and Langer, Thorsten and van der Kooi, AnneandLode L. F. and Uitterlinden, Andre G. and de Vries, Andrica and Kuehni, Claudia E. and Garre, Maria L. and Kepák, Tomáš and Kruseova, Jarmila and Winther, Jeanette F. and Kremer, Leontien C. and van Dulmenandden Broeder, Eline and Tissing, Wim J. E. and Rechnitzer, Catherine and Kenborg, Line and Hasle, Henrik and Grabow, Desiree and Parfitt, Ross and Binder, Harald and Carleton, Bruce C. and Byrne, Julianne and Kaatsch, Peter and ZehnhoffandDinnesen, Antoinette Am and Zolk, Oliver and van den HeuvelandEibrink, Marry M.},
   article_location = {TORONTO},
   article_number = {3},
   doi = {http://dx.doi.org/10.2196/11868},
   keywords = {ototoxicity; hearing loss; childhood cancer survivors; cisplatin; genetics; GWAS; candidate genes; polymorphisms},
   language = {eng},
   issn = {1929-0748},
   journal = {JMIR RESEARCH PROTOCOLS},
   title = {Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study},
   url = {http://dx.doi.org/10.2196/11868},
   volume = {8},
   year = {2019}
}

TY  - JOUR
ID  - 1612356
AU  - Clemens, Eva - Meijer, Annelot J. M. - Broer, Linda - Langer, Thorsten - van der Kooi, Anne-Lode L. F. - Uitterlinden, Andre G. - de Vries, Andrica - Kuehni, Claudia E. - Garre, Maria L. - Kepák, Tomáš - Kruseova, Jarmila - Winther, Jeanette F. - Kremer, Leontien C. - van Dulmen-den Broeder, Eline - Tissing, Wim J. E. - Rechnitzer, Catherine - Kenborg, Line - Hasle, Henrik - Grabow, Desiree - Parfitt, Ross - Binder, Harald - Carleton, Bruce C. - Byrne, Julianne - Kaatsch, Peter - Zehnhoff-Dinnesen, Antoinette Am - Zolk, Oliver - van den Heuvel-Eibrink, Marry M.
PY  - 2019
TI  - Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study
JF  - JMIR RESEARCH PROTOCOLS
VL  - 8
IS  - 3
SP  - 1-11
EP  - 1-11
PB  - JMIR PUBLICATIONS, INC
SN  - 19290748
KW  - ototoxicity
KW  - hearing loss
KW  - childhood cancer survivors
KW  - cisplatin
KW  - genetics
KW  - GWAS
KW  - candidate genes
KW  - polymorphisms
UR  - http://dx.doi.org/10.2196/11868
L2  - http://dx.doi.org/10.2196/11868
N2  - Background: Survival rates after childhood cancer now reach nearly 80% in developed countries. However, treatments that lead to survival and cure can cause serious adverse effects with lifelong negative impacts on survivor quality of life. Hearing impairment is a common adverse effect in children treated with cisplatin-based chemotherapy or cranial radiotherapy. Ototoxicity can extend from high-tone hearing impairment to involvement of speech frequencies. Hearing impairment can impede speech and language and neurocognitive development. Although treatment-related risk factors for hearing loss following childhood cancer treatment have been identified, the individual variability in toxicity of adverse effects after similar treatment between childhood cancer patients suggests a role for genetic susceptibility. Currently, 12 candidate gene approach studies have been performed to identify polymorphisms predisposing to platinum-induced ototoxicity in children being treated for cancer. However, results were inconsistent and most studies were underpowered and/or lacked replication. Objective: We describe the design of the PanCareLIFE consortium's work packages that address the genetic susceptibility of platinum-induced ototoxicity. Methods: As a part of the PanCareLIFE study within the framework of the PanCare consortium, we addressed genetic susceptibility of treatment-induced ototoxicity during and after childhood cancer treatment in a large European cohort by a candidate gene approach and a genome-wide association screening. Results: This study included 1124 survivors treated with cisplatin, carboplatin, or cranial radiotherapy for childhood cancer, resulting in the largest clinical European cohort assembled for this late effect to date. Within this large cohort we defined a group of 598 cisplatin-treated childhood cancer patients not confounded by cranial radiotherapy. The PanCareLIFE initiative provided, for the first time, a unique opportunity to confirm already identified determinants for hearing impairment during childhood cancer using a candidate gene approach and set up the first international genome-wide association study of cisplatin-induced direct ototoxicity in childhood cancer patients to identify novel allelic variants. Results will be validated in an independent replication cohort. Patient recruitment started in January 2015 and final inclusion was October 2017. We are currently performing the analyses and the first results are expected by the end of 2019 or the beginning of 2020. Conclusions: Genetic factors identified as part of this pan-European project, PanCareLIFE, may contribute to future risk prediction models that can be incorporated in future clinical trials of platinum-based therapies for cancer and may help with the development of prevention strategies.
ER  -

CLEMENS, Eva, Annelot J. M. MEIJER, Linda BROER, Thorsten LANGER, Anne-Lode L. F. VAN DER KOOI, Andre G. UITTERLINDEN, Andrica DE VRIES, Claudia E. KUEHNI, Maria L. GARRE, Tomáš KEPÁK, Jarmila KRUSEOVA, Jeanette F. WINTHER, Leontien C. KREMER, Eline VAN DULMEN-DEN BROEDER, Wim J. E. TISSING, Catherine RECHNITZER, Line KENBORG, Henrik HASLE, Desiree GRABOW, Ross PARFITT, Harald BINDER, Bruce C. CARLETON, Julianne BYRNE, Peter KAATSCH, Antoinette Am ZEHNHOFF-DINNESEN, Oliver ZOLK and Marry M. VAN DEN HEUVEL-EIBRINK. Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study. \textit{JMIR RESEARCH PROTOCOLS}. TORONTO: JMIR PUBLICATIONS, INC, 2019, vol.~8, No~3, p.~1-11. ISSN~1929-0748. Available from: https://dx.doi.org/10.2196/11868.

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