A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis
Line M. H. Schack, Elnaz Naderi, Laura Fachal, Leila Dorling, Craig Luccarini, Alison M. Dunning, Gill Barnett, Miguel Elías Aguado Barrera, Neil G. Burnet, Laura M. Calvo, Brenda Diergaarde, Tom Dudding, Alison Dunning, Fréderic Duprez, Sarah L. Kerns, Melvin C. L. Kiang, Hans Langendijk, Hisham Mehanna, Andy Ness, Adelene Y. L. Sim, An Spiessens, Holly R. Summersgill, Juan F. Tajes, Ana Vega, Ceilidh Welsh, Enya O. H. Wen, Catharine West, The Danish Head and Neck Cancer Group (DAHANCA), Enya H. W. Ong, Melvin L. K. Chua, Johannes A. Langendijk, Behrooz Z. Alizadeh, Jens Overgaard, Jesper Grau Eriksen, Christian Nicolaj Andreassen, Jan Alsner
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: ). 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.