期刊
BRITISH JOURNAL OF CANCER
卷 126, 期 7, 页码 1082-1090出版社
SPRINGERNATURE
DOI: 10.1038/s41416-021-01670-w
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资金
- CIRRO-The Lundbeck Foundation Center for Interventional Research in Radiation Oncology
- Danish Council for Strategic Research
- Aarhus University
- Danish Cancer Society [R17-A776-09-S10, R20-A1040-10-S2, R90-A6300-14-S2]
- Radiumstationens Forskningsfond
- Helga and Peter Kornings Fond
This study conducted a two-stage genome-wide association study on head and neck cancer patients, identifying and replicating a genetic locus associated with mucositis.
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; p(pooled) = 4.34 x 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.
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