SynthesisPLoS genetics2021
Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers.
Abstract readMeta-Analysis
In one paragraph
Synthesis in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 3 pooled it
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.Nature communications · 2024Pooled it
- Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.Nature communications · 2023Pooled it
- Genetic Analysis of Lung Cancer and the Germline Impact on Somatic Mutation Burden.Journal of the National Cancer Institute · 2022Pooled it
- Associations of combined lifestyle and genetic risk with incident head and neck cancer: a prospective study in the UK Biobank.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
- Development and validation of an immune-related diagnostic signature for breast cancer bone metastasis.Scientific reports · 2026Article
- Cross-ancestral GWAS identifies 29 variants across head and neck cancer subsites.Nature communications · 2025Article
- Donor genetics and storage conditions influence mitochondrial DNA and extracellular vesicle levels in RBC units.JCI insight · 2025Article
- Mapping chromatin interactions at melanoma susceptibility loci uncovers distant cis-regulatory gene targets.American journal of human genetics · 2025Article
- Novel risk loci encompassing genes influencing STAT3, GPCR, and oxidative stress signaling are associated with co-morbid GERD and COPD.PLoS genetics · 2025Article
- Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension.Circulation · 2024Article
- Mutations found in cancer patients compromise DNA binding of the winged helix protein STK19.Scientific reports · 2024Article
- Common and novel haplotype structures between different types of cancer.Cancer reports (Hoboken, N.J.) · 2024Article
- Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers.Nature communications · 2024Article
- The expression and biological role of complement C1s in esophageal squamous cell carcinoma.Open life sciences · 2024Article
- Low expression of PINK1 and PARK2 predicts poor prognosis in patients with esophageal squamous cell carcinoma.World journal of surgical oncology · 2023Article
- The Long Non-Coding RNA ANRIL in Cancers.Cancers · 2023Review
- Immunogenetic Determinants of Susceptibility to Head and Neck Cancer in the Million Veteran Program Cohort.Cancer research · 2023Article
- Selecting the appropriate hurdles and endpoints for pentilludin, a novel antiaddiction pharmacotherapeutic targeting the receptor type protein tyrosine phosphatase D.Frontiers in psychiatry · 2023Review
- Functional studies of lung cancer GWAS beyond association.Human molecular genetics · 2022Review
- Approach to Localized Squamous Cell Cancer of the Esophagus.Current treatment options in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
53 authors.
Corina LesseurSection of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.ORCID 0000-0001-6744-6750
Aida Ferreiro-IglesiasSection of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.
James D McKaySection of Genetics, Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.
Yohan BosséDepartment of Molecular Medicine, Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec City, Canada.ORCID 0000-0002-3067-3711
Mattias JohanssonSection of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.
Valerie GaborieauSection of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.ORCID 0000-0002-0210-5215
Maria Teresa LandiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
David C ChristianiDepartment of Environmental Health, Harvard TH Chan School of Public Health, Massachusetts General Hospital, Boston, Massachusetts, United States of America.ORCID 0000-0002-0301-0242
Neil C CaporasoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0001-7562-4609
Stig E BojesenCopenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen, Denmark.ORCID 0000-0002-4061-4133
Christopher I AmosDepartment of Medicine, Baylor college of Medicine, Houston, Texas, United States of America.ORCID 0000-0002-8540-7023
Sanjay SheteDepartment of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Geoffrey LiuLunenfeld-Tanenbaum Research Institute of Sinai Health System, University of Toronto, Toronto, Canada.
Gadi RennertClalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.ORCID 0000-0002-8512-068X
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Melinda C AldrichDepartment of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.ORCID 0000-0003-3833-8448
Adonina TardonFaculty of Medicine, University of Oviedo and CIBERESP, Oviedo, Spain.
Chu ChenDepartment of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington, United States of America.ORCID 0000-0003-2267-8050
Liloglou TriantafillosInstitute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0003-0460-1404
John K FieldInstitute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0003-3951-6365
Marion Dawn TeareSchool of Health and Related Research, University Of Sheffield, Sheffield, United Kingdom.ORCID 0000-0003-3994-0051
Lambertus A KiemeneyRadboud University Medical Center, Nijmegen, The Netherlands.ORCID 0000-0002-2368-1326
Brenda DiergaardeDepartment of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Robert L FerrisUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Shanbeh ZienolddinyNational Institute of Occupational Health, Oslo, Norway.
Stephen LamBritish Columbia Cancer Agency, Vancouver, Canada.ORCID 0000-0002-3964-1492
Andrew F OlshanDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Mark C WeisslerDepartment of Otolaryngology/Head and Neck Surgery, UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Martin LackoDepartment of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.ORCID 0000-0003-2868-4822
Angela RischUniversity of Salzburg, Department of Biosciences and Cancer Cluster Salzburg, Salzburg, Austria.ORCID 0000-0002-8026-5505
Heike BickeböllerDepartment of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.ORCID 0000-0002-3361-5488
Andy R NessNational Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom.
Steve ThomasBristol Dental School, University of Bristol, Bristol, United Kingdom.
Loic Le MarchandEpidemiology Program, University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii, United States of America.
Matthew B SchabathDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.ORCID 0000-0003-3241-3216
Victor Wünsch-FilhoFaculdade de Saúde Pública, Universidade de São Paulo, São Paulo, Brazil.
Eloiza H TajaraDepartment of Molecular Biology, School of Medicine of São José do Rio Preto, São José do Rio Preto, Brazil.ORCID 0000-0002-2603-2057
Angeline S AndrewBiomedical Data Science, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, United States of America.
Gary M CliffordInfections Section, Infections and Cancer Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.ORCID 0000-0001-7534-333X
Philip LazarusDepartment of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington, United States of America.ORCID 0000-0002-8686-0874
Kjell GrankvistDepartment of Medical Biosciences, Umeå University, Umeå, Sweden.ORCID 0000-0003-4289-2097
Mikael JohanssonDepartment of Radiation Sciences, Umeå University, Umeå, Sweden.ORCID 0000-0003-4182-8923
Susanne ArnoldMarkey Cancer Center, University of Kentucky, Lexington, Kentucky, United States of America.ORCID 0000-0001-6542-9551
Olle MelanderDepartment of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Hans BrunnströmDepartment of Clinical Sciences, Lund University, Lund, Sweden.ORCID 0000-0001-7402-138X
Stefania BocciaSection of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia.ORCID 0000-0002-1864-749X
Gabriella CadoniDipartimento Patologia Testa Collo e Organi di Senso, Istituto di Clinica Otorinolaringoiatrica, Università Cattolica del Sacro Cuore, Roma, Italia.
Wim TimensDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-4146-6363
Ma'en ObeidatCentre for Heart Lung Innovation, St Paul's Hospital, The University of British Columbia, Vancouver, Canada.ORCID 0000-0002-5443-2752
Xiangjun XiaoDepartment of Medicine, Baylor college of Medicine, Houston, Texas, United States of America.
Richard S HoulstonDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-5268-0242
Rayjean J HungProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.ORCID 0000-0002-4486-7496
Paul BrennanSection of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.ORCID 0000-0002-0518-8714
Funding
VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0MTRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5MUNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI GIBBONS, DON LYNN · 1996 to 2024
$57.4MWILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 2004 to 2026
$49.6MThe Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4MUniversity of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI KATHLEEN L. O'CONNOR · 2013 to 2026
$38.3MUnderstanding Population Differences in Cancer: The MEC StudyU01CA164973 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI HAIMAN, CHRISTOPHER ALAN, LE MARCHAND, LOIC · 2015 to 2025
$37.4MTranslating Molecular and Clinical Data to Population Lung Cancer Risk AssessmentU19CA203654 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Christopher I. Amos, Rayjean J. Hung · 2017 to 2026
$23.7MGENETIC SUSCEPTIBILITY TO CANCER IN MULTIETHNIC COHORTSR01CA063464 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2001 to 2005
$23.2MTHE ROLE OF CAL IN CIF-MEDIATED DEGRADATION OF CFTRP20RR018787 · NCRR · DARTMOUTH COLLEGE · PI STANTON, BRUCE A. · 2003 to 2011
$21.9MVALIDATION OF A DIET HISTORY METHOD FOR EPIDEMIOLOGIC STUDIES OF CANCERP01CA033619 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI KOLONEL, LAURENCE N. · 1985 to 2010
$18.5MKentucky Center for Clinical and Translational ScienceUL1TR000117 · NCATS · UNIVERSITY OF KENTUCKY · PI KERN, PHILIP A · 2012 to 2015
$13.3MCancer Research UKDepartment of Health RP-PG-0707-10034NCATS NIH HHS UL1 TR000117NCATS NIH HHS UL1 TR000445NCI NIH HHS K07 CA172294NCI NIH HHS P01 CA033619NCI NIH HHS P20 CA090578NCI NIH HHS P30 CA047904NCI NIH HHS P30 CA076292NCI NIH HHS P30 CA177558NCI NIH HHS P50 CA070907NCI NIH HHS P50 CA090578NCI NIH HHS P50 CA097190NCI NIH HHS P50 CA119997NCI NIH HHS R01 CA063464NCI NIH HHS R01 CA074386NCI NIH HHS R01 CA090731NCI NIH HHS R01 CA092824NCI NIH HHS R01 CA111703NCI NIH HHS R01 CA151989NCI NIH HHS R01 CA176568NCI NIH HHS U01 CA063464NCI NIH HHS U01 CA164973NCI NIH HHS U01 CA167462NCI NIH HHS U19 CA148127NCI NIH HHS U19 CA203654NCI NIH HHS UM1 CA164973NCI NIH HHS UM1 CA167462NCRR NIH HHS P20 RR018787NCRR NIH HHS S10 RR025141NHGRI NIH HHS U01 HG004798NIDCR NIH HHS R01 DE025712NIH HHS S10 OD025092World Health Organization 001
Abstract
Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.
Indexed as
Genetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyAllelesBiomarkers, TumorCarcinoma, Squamous CellDigestive System NeoplasmsGenotypeHumansOdds RatioSignal TransductionBiomarkers, Tumor
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC0
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.