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Cross-ancestral GWAS identifies 29 variants across head and neck cancer subsites.
Ebrahimi, E. ; Sangphukieo, A. ; Park, H. A. ; Gaborieau, V. ; Ferreiro-Iglesias, A. ; Diergaarde, B. ; Ahrens, W. ; Alemany, L. ; Arantes, L. M. ; Betka, J. ; Bratman, S. V. ; Canova, C. ; Conlon, M. S. ; Conway, D. I. ; Cuello, M. ; Curado, M. P. ; de Carvalho, A. C. ; de Oliviera, J. C. ; Gormley, M. ; Hadji, M. ; Hargreaves, S. ; Healy, C. M. ; Holcatova, I. ; Hung, R. J. ; Kowalski, L. P. ; Lagiou, P. ; Lagiou, A. ; Liu, G. ; Macfarlane, G. J. ; Olshan, A. F. ; Perdomo, S. ; Pinto, L. F. R. ; Podesta, J. R. V. ; Polesel, J. ; Pring, M. ; Rashidian, H. ; Gama, R. R. ; Richiardi, L. ; Robinson, M. ; Rodriguez-Urrego, P. A. ; Santi, S. A. ; Saunders, D. P. ; Soares-Lima, S. C. ; Timpson, N. ; Vilensky, M. ; von Zeidler, S. V. ; Waterboer, T.DKFZ* ; Zendehdel, K. ; Znaor, A. ; Brennan, P. ; Consortium, H. (Collaboration Author) ; McKay, J. ; Virani, S. ; Dudding, T. ; de Carvalho, A. C. (Contributor) ; de Oliviera, J. C. (Contributor) ; Pinto, L. F. (Contributor) ; Timpson, N. (Contributor) ; von Zeidler, S. V. (Contributor) ; Adam, R. (Contributor) ; Agudo, A. (Contributor) ; Alibhai, S. (Contributor) ; AlWaheidi, S. F. (Contributor) ; Pavon, M. A. (Contributor) ; Anwar, N. (Contributor) ; Arantes, P. E. (Contributor) ; Arguello, L. (Contributor) ; Avello, Y. (Contributor) ; Avondet, L. (Contributor) ; Baldión-Elorza, A. M. (Contributor) ; Daniel, C. B. (Contributor) ; Beraldi, B. (Contributor) ; Berenstein, B. (Contributor) ; Bernal, P. (Contributor) ; Rodrigues, N. B. (Contributor) ; Zimmermann, J. B. (Contributor) ; Botta, M. G. (Contributor) ; Bouvard, L. (Contributor) ; Brenes, J. (Contributor) ; Brenner, N. (Contributor)DKFZ* ; Brentisci, C. (Contributor) ; Burtica, C. (Contributor) ; Cabañas, M. L. (Contributor) ; Cantor, E. (Contributor) ; Carvalho, R. S. (Contributor) ; Carvalho, A. L. (Contributor) ; Chiusa, L. (Contributor) ; Chopard, P. (Contributor) ; Chundriger, Q. (Contributor) ; Clavero, O. (Contributor) ; Costa, I. (Contributor) ; Creaney, G. (Contributor) ; Cuffini, C. (Contributor) ; Dias, T. C. (Contributor) ; de Souza, E. D. (Contributor) ; Durant, L. C. (Contributor) ; Escallón, A. (Contributor) ; Fernandes, G. A. (Contributor) ; Fervers, B. (Contributor) ; Fiano, V. (Contributor) ; Figueira, F. F. (Contributor) ; Villefort, R. F. (Contributor) ; Gangemi, M. (Contributor) ; Garzino-Demo, P. (Contributor) ; Gholipour, M. (Contributor) ; Giglio, R. (Contributor) ; Goulart, M. A. (Contributor) ; Sant'Anna, J. G. (Contributor) ; Grega, M. (Contributor) ; Có, A. C. G. (Contributor) ; Guasch, A. (Contributor) ; Hakim, J. A. (Contributor) ; Hayes, D. N. (Contributor) ; de Sá Santos, M. H. (Contributor) ; Hurley, K. (Contributor) ; Insfran, M. (Contributor) ; Iorio, G. C. (Contributor) ; Siddiqui, M. I. (Contributor) ; Johannsen, J. (Contributor) ; Kaňa, M. (Contributor) ; Klussmann, J. P. (Contributor) ; Legal, E. (Contributor) ; Lenzi, J. (Contributor) ; Dias, F. L. (Contributor) ; González, I. L. (Contributor) ; Zorzaneli, W. M. (Contributor) ; Rocha, R. M. (Contributor) ; Mañós, M. (Contributor) ; de Abreu, P. M. (Contributor) ; Marzban, M. (Contributor) ; McCaul, J. (Contributor) ; McMahon, A. D. (Contributor) ; Mena, C. (Contributor) ; Mendonça, E. F. (Contributor) ; Mendoza, L. (Contributor) ; Meza, L. (Contributor) ; Michels, B. (Contributor) ; Mineiro, M. S. (Contributor) ; Moccia, C. (Contributor) ; Mongelos, P. (Contributor) ; Montealegre-Páez, A. L. (Contributor) ; Cortes, F. M. (Contributor) ; Muñoz, A. (Contributor) ; Ness, A. (Contributor) ; Neves, A. B. (Contributor) ; Oliva, M. (Contributor) ; de Oliveira, J. C. (Contributor) ; Ortiz, H. (Contributor) ; Ortiz, J. (Contributor) ; Osorio, M. (Contributor) ; Ospina, V. (Contributor) ; Ostellino, O. (Contributor) ; Palau, M. (Contributor) ; Paterson, C. (Contributor) ; Casabona, S. P. (Contributor) ; Pecorari, G. (Contributor) ; Pereira, D. M. (Contributor) ; Pérol, O. (Contributor) ; Pervez, S. (Contributor) ; Pomata, A. (Contributor) ; Popovic, M. (Contributor) ; Poveda, A. (Contributor) ; Prado, C. P. (Contributor) ; Prager, K. M. (Contributor) ; Ramieri, G. (Contributor) ; Rasul, S. (Contributor) ; Rego, J. N. (Contributor) ; Reis, R. M. (Contributor) ; Renard, H. (Contributor) ; Ricardi, U. (Contributor) ; Riva, G. (Contributor) ; Rodilla, F. (Contributor) ; Rodriguez, I. (Contributor) ; Rodríguez, M. I. (Contributor) ; Ross, A. (Contributor) ; Roux, P.-E. (Contributor) ; Ali, T. S. (Contributor) ; Saintigny, P. (Contributor) ; Santivañez, J. J. (Contributor) ; Scapultampo-Neto, C. (Contributor) ; Segovia, J. (Contributor) ; Sena, A. (Contributor) ; Serrano, R. (Contributor) ; Sharma, S. J. (Contributor) ; Siefer, O. (Contributor) ; Smart, S. (Contributor) ; Sorroche, B. P. (Contributor) ; Sosa, C. (Contributor) ; de Oliveira, J. S. (Contributor) ; Stura, A. (Contributor) ; Thomas, S. (Contributor) ; Torres, O. (Contributor) ; Tous, S. (Contributor) ; Ucross, G. (Contributor) ; Valenzuela, A. (Contributor) ; de Podestá, J. R. V. (Contributor) ; Whitmarsh, A. (Contributor) ; Wright, S. (Contributor)
2025
Springer Nature
[London]
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Please use a persistent id in citations: doi:10.1038/s41467-025-63842-z
Abstract: Head and neck squamous cell carcinoma (HNSCC) includes diverse cancers arising in the oral cavity, oropharynx, and larynx, with the main risk factors being environmental exposures such as tobacco, alcohol, and human papillomavirus (HPV) infection. The genetic factors contributing to susceptibility across different populations and tumour subsites remain incompletely understood. Here we show, through a genome-wide association and fine mapping study of over 19,000 HNSCC cases and 38,000 controls from multiple ancestries, 18 genetic risk variants and 11 signals from fine mapping of the human leukocyte antigen (HLA) region, all previously unreported. rs78378222, a regulatory variant for TP53 is associated with a 40% reduction in overall HNSCC risk. We also identify gene-environment interactions, with BRCA2 and ADH1B variants showing effects modified by smoking and alcohol use. Subsite-specific analysis of the HLA region reveals distinct immune-related associations across HPV-positive and HPV-negative tumours. These findings refine the genetic architecture of HNSCC and highlight mechanisms linking inherited variation, immunity, and environmental exposures.
Keyword(s): Humans (MeSH) ; Genome-Wide Association Study (MeSH) ; Head and Neck Neoplasms: genetics (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Squamous Cell Carcinoma of Head and Neck: genetics (MeSH) ; Polymorphism, Single Nucleotide (MeSH) ; Papillomavirus Infections: genetics (MeSH) ; Papillomavirus Infections: complications (MeSH) ; Female (MeSH) ; Gene-Environment Interaction (MeSH) ; BRCA2 Protein: genetics (MeSH) ; Male (MeSH) ; Alcohol Dehydrogenase: genetics (MeSH) ; Alcohol Drinking (MeSH) ; Tumor Suppressor Protein p53: genetics (MeSH) ; Smoking: adverse effects (MeSH) ; Risk Factors (MeSH) ; Middle Aged (MeSH) ; Case-Control Studies (MeSH) ; HLA Antigens: genetics (MeSH) ; Carcinoma, Squamous Cell: genetics (MeSH) ; BRCA2 Protein ; ADH1B protein, human ; Alcohol Dehydrogenase ; Tumor Suppressor Protein p53 ; BRCA2 protein, human ; TP53 protein, human ; HLA Antigens
Contributing Institute(s):
- Infektionen und Krebs-Epidemiologie (D320)
Research Program(s):
- 314 - Immunologie und Krebs (POF4-314) (POF4-314)
Appears in the scientific report
2025
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