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A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review


  • Line M H Schack
  • Elnaz Naderi, University of Groningen
  • ,
  • Laura Fachal, University of Cambridge
  • ,
  • Leila Dorling, University of Cambridge
  • ,
  • Craig Luccarini, University of Cambridge
  • ,
  • Alison M Dunning, University of Cambridge
  • ,
  • The Head and Neck Group of the Radiogenomics Consortium
  • ,
  • The Danish Head and Neck Cancer Group (DAHANCA)
  • ,
  • Enya H W Ong, University of Dundee
  • ,
  • Melvin L K Chua, Division of Medical Physics in Radiation Oncology
  • ,
  • Johannes A Langendijk, University of Groningen
  • ,
  • Behrooz Z Alizadeh, University of Groningen
  • ,
  • Jens Overgaard
  • Jesper Grau Eriksen
  • Christian Nicolaj Andreassen
  • Jan Alsner

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.

TidsskriftBritish Journal of Cancer
Sider (fra-til)1082-1090
Antal sider9
StatusUdgivet - apr. 2022

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