ArticleNature communications2025
Cross-ancestral GWAS identifies 29 variants across head and neck cancer subsites.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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11citing papers in PubMed, 1 pooled it
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A genome-wide association study of buccal mucosa cancer in India and multi-ancestry meta-analysis discovers risk loci and gene-environment interactions.EBioMedicine · 2025Pooled it
- Genetic susceptibility, risk prediction, and druggable targets for oropharyngeal cancer: a UK Biobank study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Review
- A pan-cancer functional atlas of ADH1A reveals its conserved role in the tumor microenvironment and immunity.Translational cancer research · 2026Article
- Genome-wide association study of never-smoking non-drinking young adults developing oral squamous cell carcinoma.BMC cancer · 2026Article
- Early Cancer Detection: What's Going on and What's Next.MedComm · 2026Review
- Nanomedicine as an opportunity for equity achievements through cost-reduction in public healthcare for head and neck cancer treatment in Brazil.BMC health services research · 2026Article
- Metachronous triple primary malignancies of duodenum, skin, and appendix in the absence of common hereditary syndromes: a case report.American journal of cancer research · 2026Article
- Reassessing the link between adiposity and head and neck cancer: a Mendelian randomization study.eLife · 2025Article
- Proteogenomic and observational evidence implicate ANGPTL4 as a potential therapeutic target for colorectal cancer prevention.Journal of the National Cancer Institute · 2025Article
- VOYAGER: an international consortium investigating the role of human papilloma virus and genetics in oral and oropharyngeal cancer risk and survival.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
- Update of
Authors and funding
54 authors.
Elmira EbrahimiGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.ORCID http://orcid.org/0000-0003-0910-3447
Apiwat SangphukieoGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Hanla A ParkGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.ORCID http://orcid.org/0000-0001-8055-3729
Valerie GaborieauGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Aida Ferreiro-IglesiasGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Brenda DiergaardeDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, USA.
Wolfgang AhrensLeibniz Institute for Prevention Research and Epidemiology-BIPS, Bremen, Germany.ORCID http://orcid.org/0000-0003-3777-570X
Laia AlemanyCatalan Institute of Oncology. ICO, L'Hospitalet, Barcelona, Spain.
Lidia Mrb ArantesBarretos Cancer Hospital, Barretos, Brazil.
Jaroslav BetkaDepartment of Otorhinolarygology and Head And Neck Surgery, 1.st Medical Faculty, Charles University, Faculty Hospital Motol, Prague, Czech Republic.
Scott V BratmanDepts of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
Cristina CanovaUnit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padova, Padova, Italy.
Michael Sc ConlonEpidemiology, Outcomes & Evaluation Research, Health Sciences North Research Institute, Sudbury, Canada.
David I ConwaySchool of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK.
Mauricio CuelloOncology, Hospital de Clinicas Dr. Manuel Quintela, Montevideo, Uruguay.
Maria Paula CuradoEpidemiology and Statistics Group, Research Center, A.C Camargo Cancer Center, São Paulo, Brazil.ORCID http://orcid.org/0000-0001-8172-2483
Ana Carolina de CarvalhoGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Jose Carlos de OlivieraAraújo Jorge Cancer Hospital, Associação de Combate ao Câncer em Goiás, Goiania, Brazil.
Mark GormleyBristol Dental School, Bristol University, Bristol, UK.ORCID http://orcid.org/0000-0001-5733-6304
Maryam HadjiCancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran.
Sarah HargreavesUniversity Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.ORCID http://orcid.org/0000-0002-8272-5915
Claire M HealySchool of Dental Science, Dublin Dental University Hospital, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0003-0583-6360
Ivana HolcatovaInstitute of Hygiene & Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.ORCID http://orcid.org/0000-0002-1366-0337
Rayjean J HungProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.ORCID http://orcid.org/0000-0002-4486-7496
Luis P KowalskiDepartment of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil.ORCID http://orcid.org/0000-0002-0481-156X
Pagona LagiouDepartment of Hygiene, Epidemiology & Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Areti LagiouDepartment of Public and Community Health, School of Public Health, University of West Attica, Athens, Greece.
Geoffrey LiuMedicine, Epidemiology, Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
Gary J MacfarlaneEpidemiology Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
Andrew F OlshanDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA.
Sandra PerdomoGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.ORCID http://orcid.org/0000-0001-7740-8141
Luis Felipe Ribiero PintoPrograma de Carcinogênese Molecular, Instituto Nacional de Câncer - INCA, Rio de Janeiro, Brazil.
Jose Roberto V PodestaHead and Neck Surgery Division, Women's Association for Education and Fight Against Cancer/AFECC, Vitória, Brazil.ORCID http://orcid.org/0000-0001-6995-955X
Jerry PoleselUnit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.ORCID http://orcid.org/0000-0001-9381-1520
Miranda PringBristol Dental School, Bristol University, Bristol, UK.
Hamideh RashidianCancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran.
Ricardo R GamaDepartment of Head and Neck Surgery, Barretos Cancer Hospital, São Paulo, Brazil.ORCID http://orcid.org/0000-0003-4406-8958
Lorenzo RichiardiCancer Epidemiology Unit, University of Turin, Turin, Italy.ORCID http://orcid.org/0000-0003-0316-9402
Max RobinsonCellular Pathology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-4491-6865
Paula A Rodriguez-UrregoPathology and Laboratories, Pathology, University Hospital Fundacion Santa Fe de Bogota, Bogota, Colombia.ORCID http://orcid.org/0000-0003-3693-7690
Stacey A SantiClinical Oncology Research, Health Sciences North Research Institute, Sudbury, Canada.
Deborah P SaundersDepartment of Dental Oncology, Health Sciences North, Northern Ontario School of Medicine University, Sudbury, Canada.
Sheila C Soares-LimaBrazilian National Cancer Institute, Rio de Janeiro, Brazil.ORCID http://orcid.org/0000-0002-6742-3708
Nicholas TimpsonMRC Integrative Epidemiology Unit, Bristol University, Bristol, UK.ORCID http://orcid.org/0000-0002-7141-9189
Marta VilenskyInstituto de Oncologia Angel H Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina.
Sandra V von ZeidlerPathology Department, Federal University of Espírito Santo, Vitória, Brazil.ORCID http://orcid.org/0000-0002-8897-5747
Tim WaterboerInfections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-0616-6963
Kazem ZendehdelCancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran.
Ariana ZnaorCancer Surveillance Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.ORCID http://orcid.org/0000-0002-5849-4782
Paul BrennanGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
HEADSpAcE Consortium
James McKayGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Shama Virani *Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France. viranis@iarc.who.int.ORCID http://orcid.org/0000-0002-1163-432X
Tom Dudding *Bristol Dental School, Bristol University, Bristol, UK. tom.dudding@bristol.ac.uk.ORCID http://orcid.org/0000-0003-3756-040X
Funding
VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0MWILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Heath Devin Skinner · 2004 to 2026
$49.6MGene Environment Interaction in Head and Neck CancerR01CA090731 · NCI · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI OLSHAN, ANDREW · 2001 to 2005
$4.6MThe role of germline and somatic DNA mutations in oral and oropharyngeal cancersR01DE025712 · NIDCR · INTERNATIONAL AGENCY FOR RES ON CANCER · PI BRENNAN, PAUL JOSEPH, DIERGAARDE, BRENDA B. · 2017 to 2021
$3.3MGermline risk of oral and oropharyngeal cancers across diverse populationsR03DE030257 · NIDCR · INTERNATIONAL AGENCY FOR RES ON CANCER · PI VIRANI, SHAMA · 2021 to 2022
$222kNCI NIH HHS P30 CA047904NCI NIH HHS P50 CA097190NCI NIH HHS R01 CA090731NIDCR NIH HHS R01 DE025712NIDCR NIH HHS R03 DE030257Wellcome TrustWorld Health Organization 001
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.
Indexed as
Carcinoma, Squamous CellHead and Neck NeoplasmsSquamous Cell Carcinoma of Head and NeckAlcohol DehydrogenaseAlcohol DrinkingBRCA2 ProteinCase-Control StudiesFemaleGene-Environment InteractionGenetic Predisposition to DiseaseGenome-Wide Association StudyHLA AntigensHumansMaleMiddle AgedPapillomavirus InfectionsADH1B protein, humanAlcohol DehydrogenaseBRCA2 ProteinBRCA2 protein, humanHLA AntigensTP53 protein, humanTumor Suppressor Protein p53
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