• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Meta-GWAS identifies the heritability of acute radiation-induced toxicities in head and neck cancer

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    36191651.pdf
    Size:
    2.014Mb
    Format:
    PDF
    Description:
    Identified with Open Access button
    Download
    Authors
    Naderi, E.
    Schack, L. M. H.
    Welsh, C.
    Sim, A. Y. L.
    Aguado-Barrera, M. E.
    Dudding, T.
    Summersgil, Holly
    Martínez-Calvo, L.
    Ong, E. H. W.
    Odding, Y.
    Varela-Pazos, A.
    Steenbakkers, R.
    Crijns, A. P. G.
    Jena, R.
    Pring, M.
    Dennis, J.
    Lobato-Busto, R.
    Alsner, J.
    Ness, A.
    Nutting, C.
    Thomson, David J
    Gómez-Caamaño, A.
    Eriksen, J. G.
    Thomas, S. J.
    Bates, A. M.
    Overgaard, J.
    Cascallar-Caneda, L. M.
    Duprez, F.
    Barnett, G. C.
    Dorling, L.
    M, L. K. C.
    Vega, A.
    West, Catharine M L
    Langendijk, J. A.
    Nicolaj Andreassen, C.
    Alizadeh, B. Z.
    Show allShow less
    Affiliation
    Department of Radiation Oncology, University Medical Center Groningen, Groningen, The Netherlands; Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands
    Issue Date
    2022
    
    Metadata
    Show full item record
    Abstract
    Background and purpose: We aimed to the genetic components and susceptibility variants associated with acute radiation-induced toxicities (RITs) in patients with head and neck cancer (HNC). Materials and methods: We performed the largest meta-GWAS of seven European cohorts (n = 4,042). Patients were scored weekly during radiotherapy for acute RITs including dysphagia, mucositis, and xerostomia. We analyzed the effect of variants on the average burden (measured as area under curve, AUC) per each RIT, and standardized total average acute toxicity (STATacute) score using a multivariate linear regression. We tested suggestive variants (p < 1.0x10-5) in discovery set (three cohorts; n = 2,640) in a replication set (four cohorts; n = 1,402). We meta-analysed all cohorts to calculate RITs specific SNP-based heritability, and effect of polygenic risk scores (PRSs), and genetic correlations among RITS. Results: From 393 suggestive SNPs identified in discovery set; 37 were nominally significant (preplication < 0.05) in replication set, but none reached genome-wide significance (pcombined < 5 × 10-8). In-silico functional analyses identified "3'-5'-exoribonuclease activity" (FDR = 1.6e-10) for dysphagia, "inositol phosphate-mediated signalling" for mucositis (FDR = 2.20e-09), and "drug catabolic process" for STATacute (FDR = 3.57e-12) as the most enriched pathways by the RIT specific suggestive genes. The SNP-based heritability (±standard error) was 29 ± 0.08 % for dysphagia, 9 ± 0.12 % (mucositis) and 27 ± 0.09 % (STATacute). Positive genetic correlation was rg = 0.65 (p = 0.048) between dysphagia and STATacute. PRSs explained limited variation of dysphagia (3 %), mucositis (2.5 %), and STATacute (0.4 %). Conclusion: In HNC patients, acute RITs are modestly heritable, sharing 10 % genetic susceptibility, when PRS explains < 3 % of their variance. We identified numerus suggestive SNPs, which remain to be replicated in larger studies.
    Citation
    Naderi E, Schack LMH, Welsh C, Sim AYL, Aguado-Barrera ME, Dudding T, et al. Meta-GWAS identifies the heritability of acute radiation-induced toxicities in head and neck cancer. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2022 Sep 30. PubMed PMID: 36191651. Epub 2022/10/04. eng.
    Journal
    Radiotherapy and Oncology
    URI
    http://hdl.handle.net/10541/625702
    DOI
    10.1016/j.radonc.2022.09.016
    PubMed ID
    36191651
    Additional Links
    https://dx.doi.org/10.1016/j.radonc.2022.09.016
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.radonc.2022.09.016
    Scopus Count
    Collections
    All Christie Publications

    entitlement

    Related articles

    • A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer.
    • Authors: Naderi E, Crijns APG, Steenbakkers RJHM, van den Hoek JGM, Boezen HM, Alizadeh BZ, Langendijk JA
    • Issue date: 2021 Nov 27
    • A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis.
    • Authors: Schack LMH, Naderi E, Fachal L, Dorling L, Luccarini C, Dunning AM, Head and Neck Group of the Radiogenomics Consortium, Danish Head and Neck Cancer Group (DAHANCA), Ong EHW, Chua MLK, Langendijk JA, Alizadeh BZ, Overgaard J, Eriksen JG, Andreassen CN, Alsner J
    • Issue date: 2022 Apr
    • Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy.
    • Authors: Dean JA, Wong KH, Gay H, Welsh LC, Jones AB, Schick U, Oh JH, Apte A, Newbold KL, Bhide SA, Harrington KJ, Deasy JO, Nutting CM, Gulliford SL
    • Issue date: 2016 Nov 15
    • Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer.
    • Authors: Antonadou D, Pepelassi M, Synodinou M, Puglisi M, Throuvalas N
    • Issue date: 2002 Mar 1
    • Patterns of dysphagia and acute toxicities in patients with head and neck cancer undergoing helical IMRT±concurrent chemotherapy.
    • Authors: Moroney LB, Helios J, Ward EC, Crombie J, Wockner LF, Burns CL, Spurgin AL, Blake C, Kenny L, Hughes BG
    • Issue date: 2017 Jan
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.