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

The Head and Neck Group of the Radiogenomics Consortium; The Danish Head and Neck Cancer Group (DAHANCA); Line M.H. Schack; Elnaz Naderi; Laura Fachal; Leila Dorling; Craig Luccarini; Alison Dunning; Brenda Diergaarde; Tom Dudding; Alison Dunning; Enya H.W. Ong; Melvin L.K. Chua; Johannes A. Langendijk; Behrooz Z. Alizadeh; Jens Overgaard; Jesper Grau Eriksen; Christian Nicolaj Andreassen; Jan Alsner

doi:10.1038/s41416-021-01670-w

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

The Head and Neck Group of the Radiogenomics Consortium, The Danish Head and Neck Cancer Group (DAHANCA), Line M.H. Schack^*, Elnaz Naderi, Laura Fachal, Leila Dorling, Craig Luccarini, Alison Dunning, Brenda Diergaarde, Tom Dudding, Alison Dunning, Enya H.W. Ong, Melvin L.K. Chua, Johannes A. Langendijk, Behrooz Z. Alizadeh, Jens Overgaard, Jesper Grau Eriksen, Christian Nicolaj Andreassen, Jan Alsner

^*Corresponding author for this work

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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; p_pooled = 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.

Original language	English
Pages (from-to)	1082-1090
Number of pages	9
Journal	British Journal of Cancer
Volume	126
Issue number	7
Early online date	17 Jan 2022
DOIs	https://doi.org/10.1038/s41416-021-01670-w
Publication status	Published - 1 Apr 2022

Bibliographical note

Funding Information:
This study was made possible by financial support from CIRRO—The Lundbeck Foundation Center for Interventional Research in Radiation Oncology, the Danish Council for Strategic Research, Aarhus University, the Danish Cancer Society (grant no. R17‐A776‐09‐S10, R20‐A1040‐10‐S2 and R90‐A6300‐14‐S2), Radiumstationens Forskningsfond and Helga and Peter Kornings Fond. Funding partners did not participate in study design, data collection, analysis or preparation of the manuscript.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

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The Head and Neck Group of the Radiogenomics Consortium, The Danish Head and Neck Cancer Group (DAHANCA), Schack, L. M. H., Naderi, E., Fachal, L., Dorling, L., Luccarini, C., Dunning, A., Diergaarde, B., Dudding, T., Dunning, A., Ong, E. H. W., Chua, M. L. K., Langendijk, J. A., Alizadeh, B. Z., Overgaard, J., Eriksen, J. G., Andreassen, C. N., & Alsner, J. (2022). A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis. British Journal of Cancer, 126(7), 1082-1090. https://doi.org/10.1038/s41416-021-01670-w

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

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.",

author = "{The Head and Neck Group of the Radiogenomics Consortium} and {The Danish Head and Neck Cancer Group (DAHANCA)} and Schack, {Line M.H.} and Elnaz Naderi and Laura Fachal and Leila Dorling and Craig Luccarini and Alison Dunning and Brenda Diergaarde and Tom Dudding and Alison Dunning and Ong, {Enya H.W.} and Chua, {Melvin L.K.} and Langendijk, {Johannes A.} and Alizadeh, {Behrooz Z.} and Jens Overgaard and Eriksen, {Jesper Grau} and Andreassen, {Christian Nicolaj} and Jan Alsner and Hisham Mehanna",

note = "Funding Information: This study was made possible by financial support from CIRRO—The Lundbeck Foundation Center for Interventional Research in Radiation Oncology, the Danish Council for Strategic Research, Aarhus University, the Danish Cancer Society (grant no. R17‐A776‐09‐S10, R20‐A1040‐10‐S2 and R90‐A6300‐14‐S2), Radiumstationens Forskningsfond and Helga and Peter Kornings Fond. Funding partners did not participate in study design, data collection, analysis or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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The Head and Neck Group of the Radiogenomics Consortium, The Danish Head and Neck Cancer Group (DAHANCA), Schack, LMH, Naderi, E, Fachal, L, Dorling, L, Luccarini, C, Dunning, A, Diergaarde, B, Dudding, T, Dunning, A, Ong, EHW, Chua, MLK, Langendijk, JA, Alizadeh, BZ, Overgaard, J, Eriksen, JG, Andreassen, CN & Alsner, J 2022, 'A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis', British Journal of Cancer, vol. 126, no. 7, pp. 1082-1090. https://doi.org/10.1038/s41416-021-01670-w

A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis. / The Head and Neck Group of the Radiogenomics Consortium; The Danish Head and Neck Cancer Group (DAHANCA); Schack, Line M.H. et al.
In: British Journal of Cancer, Vol. 126, No. 7, 01.04.2022, p. 1082-1090.

Research output: Contribution to journal › Article › peer-review

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T1 - A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis

AU - The Head and Neck Group of the Radiogenomics Consortium

AU - The Danish Head and Neck Cancer Group (DAHANCA)

AU - Schack, Line M.H.

AU - Naderi, Elnaz

AU - Fachal, Laura

AU - Dorling, Leila

AU - Luccarini, Craig

AU - Dunning, Alison

AU - Diergaarde, Brenda

AU - Dudding, Tom

AU - Dunning, Alison

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

AU - Mehanna, Hisham

N1 - Funding Information: This study was made possible by financial support from CIRRO—The Lundbeck Foundation Center for Interventional Research in Radiation Oncology, the Danish Council for Strategic Research, Aarhus University, the Danish Cancer Society (grant no. R17‐A776‐09‐S10, R20‐A1040‐10‐S2 and R90‐A6300‐14‐S2), Radiumstationens Forskningsfond and Helga and Peter Kornings Fond. Funding partners did not participate in study design, data collection, analysis or preparation of the manuscript. Publisher Copyright: © 2022, The Author(s).

PY - 2022/4/1

Y1 - 2022/4/1

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.

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The Head and Neck Group of the Radiogenomics Consortium, The Danish Head and Neck Cancer Group (DAHANCA), Schack LMH, Naderi E, Fachal L, Dorling L et al. A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis. British Journal of Cancer. 2022 Apr 1;126(7):1082-1090. Epub 2022 Jan 17. doi: 10.1038/s41416-021-01670-w

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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