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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F19%3A00070822" target="_blank" >RIV/65269705:_____/19:00070822 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/19:00112793 RIV/00216208:11130/19:10394287 RIV/00159816:_____/19:00070822 RIV/00064203:_____/19:10394287

Result on the web

<a href="https://www.researchprotocols.org/2019/3/e11868/pdf" target="_blank" >https://www.researchprotocols.org/2019/3/e11868/pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2196/11868" target="_blank" >10.2196/11868</a>

Result language

angličtina

Original language name

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

Original language description

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&apos;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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30300 - Health sciences

Project

<a href="/en/project/7E13061" target="_blank" >7E13061: PanCare Studies in Fertility and Ototoxicity to Improve Quality of Life after Cancer during Childhood, Adolescence and Young Adulthood</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

JMIR Research Protocols

ISSN

1929-0748

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

3

Country of publishing house

CA - CANADA

Number of pages

11

Pages from-to

"e11868"

UT code for WoS article

000462890300033

EID of the result in the Scopus database

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