A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis.
Authors
Naderi, Elnaz
Dorling, Leila
Luccarini, Craig
Dunning, Alison M
Head and Neck Group of the Radiogenomics Consortium
Danish Head and Neck Cancer Group (DAHANCA)
Ong, Enya HW
Langendijk, Johannes A
Eriksen, Jesper Grau
Andreassen, Christian Nicolaj
Alsner, Jan
Publication Date
2022-04Journal Title
Br J Cancer
ISSN
0007-0920
Publisher
Springer Science and Business Media LLC
Volume
126
Issue
7
Pages
1082-1090
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Schack, L. M., Naderi, E., Fachal, L., Dorling, L., Luccarini, C., Dunning, A. M., Head and Neck Group of the Radiogenomics Consortium, et al. (2022). A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis.. Br J Cancer, 126 (7), 1082-1090. https://doi.org/10.1038/s41416-021-01670-w
Description
Funder: the Danish Council for Strategic Research (grant no.R20‐A1040‐10‐S2)
Funder: the Danish Cancer Society (grant no. R90‐A6300‐14‐S2),
Abstract
PURPOSE: A two-stage genome-wide association study was carried out in head and neck cancer (HNC) patients aiming to identify genetic variants associated with either specific radiotherapy-induced (RT) toxicity endpoints or a general proneness to develop toxicity after RT. MATERIALS AND METHODS: The analysis included 1780 HNC patients treated with primary RT for laryngeal or oro/hypopharyngeal cancers. In a non-hypothesis-driven explorative discovery study, associations were tested in 1183 patients treated within The Danish Head and Neck Cancer Group. Significant associations were later tested in an independent Dutch cohort of 597 HNC patients and if replicated, summary data obtained from discovery and replication studies were meta-analysed. Further validation of significantly replicated findings was pursued in an Asian cohort of 235 HNC patients with nasopharynx as the primary tumour site. RESULTS: We found and replicated a significant association between a locus on chromosome 5 and mucositis with a pooled OR for rs1131769*C in meta-analysis = 1.95 (95% CI 1.48-2.41; ppooled = 4.34 × 10-16). CONCLUSION: This first exploratory GWAS in European cohorts of HNC patients identified and replicated a risk locus for mucositis. A larger Meta-GWAS to identify further risk variants for RT-induced toxicity in HNC patients is warranted.
Keywords
Article, /692/4028/67/1536, /692/53/2422, article
Sponsorship
European Commission FP7 Collaborative projects (CP) (608126)
Identifiers
s41416-021-01670-w, 1670
External DOI: https://doi.org/10.1038/s41416-021-01670-w
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335738
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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