TY - JOUR
T1 - A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis
AU - Schack, Line M H
AU - Naderi, Elnaz
AU - Fachal, Laura
AU - Dorling, Leila
AU - Luccarini, Craig
AU - Dunning, Alison M
AU - The Head and Neck Group of the Radiogenomics Consortium
AU - The Danish Head and Neck Cancer Group (DAHANCA)
AU - Ong, Enya H W
AU - Chua, Melvin L K
AU - Langendijk, Johannes A
AU - Alizadeh, Behrooz Z
AU - Overgaard, Jens
AU - Eriksen, Jesper Grau
AU - Andreassen, Christian Nicolaj
AU - Alsner, Jan
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Genome-Wide Association Study
KW - Head and Neck Neoplasms/genetics
KW - Humans
KW - Mucositis
KW - Radiation Oncology
UR - http://www.scopus.com/inward/record.url?scp=85122900536&partnerID=8YFLogxK
U2 - 10.1038/s41416-021-01670-w
DO - 10.1038/s41416-021-01670-w
M3 - Journal article
C2 - 35039627
SN - 0007-0920
VL - 126
SP - 1082
EP - 1090
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -