Evidence map›Paper›PMID 27527254›Full record

SynthesisThe Lancet. Oncology2016

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.

Puya Gharahkhani, Rebecca C Fitzgerald, Thomas L Vaughan, Claire Palles, Ines Gockel, Ian Tomlinson, Matthew F Buas, Andrea May, Christian Gerges, Mario Anders and 62 more

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Lancet. Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 8 pooled it
18.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

120 citing papers in PubMed, 8 syntheses or guidelines pooled it, 175 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Pooled it
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  6. Pooled it
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  9. Trial
  10. Article
  11. Article
  12. Article
  13. Article
  14. Observational
  15. Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026
    Review
  16. Article
  17. Pathogenesis of Barrett's Esophagus: Evolving and Emerging Mechanisms.Gastrointestinal endoscopy clinics of North America · 2026
    Review
  18. Article
  19. Article
  20. Prioritizing context-specific genetic risk mechanisms in 11 solid cancers.medRxiv : the preprint server for health sciences · 2025
    Article

60 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

72 authors at 20 institutions in 9 countries.

Puya GharahkhaniStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Electronic address: Puya.Gharahkhani@qimrberghofer.edu.au.
Rebecca C FitzgeraldMedical Research Council (MRC) Cancer Unit, Hutchison-MRC Research Centre and University of Cambridge, Cambridge, UK.
Thomas L VaughanDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Claire PallesWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Ines GockelDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
Ian TomlinsonWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Matthew F BuasDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Andrea MayDepartment of Medicine II, Sana Klinikum, Offenbach, Germany.
Christian GergesDepartment of Internal Medicine, Evangelisches Krankenhaus, Düsseldorf, Germany.
Mario AndersDepartment of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Klinikum, Berlin, Germany.
Jessica BeckerInstitute of Human Genetics, and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Nicole KreuserDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
Tania NoderDepartment of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Marino VeneritoDepartment of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
Lothar VeitsInstitute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
Thomas SchmidtDepartment of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Hendrik MannerDepartment of Internal Medicine II, Horst Schmidt Kliniken Hospital, Wiesbaden, Germany.
Claudia SchmidtDepartment of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
Timo HessInstitute of Human Genetics, and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Anne C BöhmerInstitute of Human Genetics, and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Jakob R IzbickiDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
Arnulf H HölscherDepartment of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
Hauke LangDepartment of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
Dietmar LorenzDepartment of General and Visceral Surgery, Sana Klinikum, Offenbach, Germany.
Brigitte SchumacherDepartment of Internal Medicine, Evangelisches Krankenhaus, Düsseldorf, Germany; Department of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.
Andreas HackelsbergerGastropraxis, Wiesbaden, Germany.
Rupert MayershoferGastroenterologie am Burgweiher, Bonn, Germany.
Oliver PechDepartment of Gastroenterology and Interventional Endoscopy, St John of God Hospital, Regensburg, Germany.
Yogesh VashistDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany; Department of Visceral Surgery, Kantonsspital Aarau AG, Aarau, Switzerland.
Katja OttDepartment of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany; Department of General, Visceral and Thorax Surgery, RoMed Klinikum Rosenheim, Rosenheim, Germany.
Michael ViethInstitute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
Josef WeismüllerGastroenterologische Gemeinschaftspraxis, Koblenz, Germany.
Markus M NöthenInstitute of Human Genetics, and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Barrett's and Esophageal Adenocarcinoma Consortium (BEACON)
Esophageal Adenocarcinoma GenEtics Consortium (EAGLE)
Wellcome Trust Case Control Consortium 2 (WTCCC2)
Stephen AttwoodCentre For Integrated Health Care Research, Durham University, Durham, UK.
Hugh BarrGloucestershire Royal Hospital, Gloucester, UK.
Laura ChegwiddenPlymouth University Peninsula School of Medicine and Dentistry, Plymouth, UK.
John de CaesteckerDigestive Diseases Centre, University Hospitals of Leicester, Leicester, UK.
Rebecca HarrisonDepartment of Cellular Pathology, Leicester Royal Infirmary, Leicester, UK.
Sharon B LoveCentre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK.
David MacDonaldDepartment of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, BC, Canada.
Paul MoayyediDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Hans PrenenDepartment of Gastroenterology, University Hospitals Gasthuisberg, Leuven, Belgium.
R G Peter WatsonQueen's University Belfast, Centre of Medical Education, Royal Victoria Hospital, Belfast, UK.
Prasad G IyerDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Lesley A AndersonCentre for Public Health, Queen's University Belfast, Belfast, UK.
Leslie BernsteinDepartment of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Wong-Ho ChowDepartment of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA.
Laura J HardieDivision of Epidemiology, University of Leeds, Leeds, UK.
Jesper LagergrenDepartment of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Division of Cancer Studies, King's College London, London, UK.
Geoffrey LiuPharmacogenomic Epidemiology, Ontario Cancer Institute, Toronto, ON, Canada.
Harvey A RischDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
Anna H WuDepartment of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Weimin YeDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Nigel C BirdDepartment of Oncology, Medical School, University of Sheffield, Sheffield, UK.
Nicholas J ShaheenDivision of Gastroenterology and Hepatology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Marilie D GammonDepartment of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Douglas A CorleyDivision of Research, and San Francisco Medical Center, Kaiser Permanente Northern California, Oakland, CA, USA.
Carlos CaldasDepartment of Oncology, and Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Susanne MoebusCentre of Urban Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, University of Essen, Essen, Germany.
Michael KnappInstitute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany.
Wilbert H M PetersDepartment of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands.
Horst NeuhausDepartment of Internal Medicine, Evangelisches Krankenhaus, Düsseldorf, Germany.
Thomas RöschDepartment of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Christian EllDepartment of Medicine II, Sana Klinikum, Offenbach, Germany.
Stuart MacGregorStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Paul PharoahCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
David C WhitemanCancer Control, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Janusz JankowskiUniversity of Central Lancashire, Westlakes Science and Technology Park, Moor Row, UK; Warwick Medical School, University of Warwick, Warwick, UK.
Johannes SchumacherInstitute of Human Genetics, and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Life & Brain (Germany) · DEQIMR Berghofer Medical Research Institute · AUSana Klinikum Offenbach · DEUniversity Medical Center Hamburg-Eppendorf · DEUniversity of Bonn · DEBayreuth Medical Center · DEEvangelisches Krankenhaus Düsseldorf · DEFred Hutch Cancer Center · USHeidelberg University · DEQueen's University Belfast · GBUniversität Hamburg · DEUniversity Hospital Leipzig · DEUniversity of Cambridge · GBUniversity of Cologne · DEUniversity of North Carolina at Chapel Hill · USCentre for Human Genetics · GBCity of Hope · USDurham University · GBElisabeth-Krankenhaus Essen · DEGloucestershire Royal Hospital · GB

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
PHYLOGENIES of Barrett's Esophagus LineagesP01CA091955 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GRADY, WILLIAM MALLORY · 2002 to 2019
$35.9M
Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study (BEAGESS)R01CA136725 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI VAUGHAN, THOMAS L, WHITEMAN, DAVID C · 2009 to 2011
$7.8M
ESTABLISHED INVESTIGATOR AWARD IN CANCER PREVENTION AND CONTROLK05CA124911 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI VAUGHAN, THOMAS L · 2007 to 2016
$1.6M
EPIDEMIOLOGY OF BARRETTS ESOPHAGUSR01CA072866 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI VAUGHAN, THOMAS L · 1997 to 2000
$543k
Cancer Research UK 10119Cancer Research UK 10124Cancer Research UK 16465Cancer Research UK 16895Cancer Research UK 16942Cancer Research UK 9675Medical Research Council MC_UU_12022/2Medical Research Council MR/M008975/1NCATS NIH HHS UL1 TR001863NCI NIH HHS K05 CA124911NCI NIH HHS P01 CA091955NCI NIH HHS R01 CA072866NCI NIH HHS R01 CA136725
6 · The paper itself

Abstract

backgroundOesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma.

methodsWe did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p<5 × 10

findingsOur sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10

interpretationOur meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies.

fundingUS National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kröner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.

Indexed as

Genome-Wide Association StudyAdenocarcinomaBarrett EsophagusEsophageal NeoplasmsHumansPolymorphism, Single NucleotideRisk

Identifiers

PMID27527254
PMCPMC5052458
OpenAlexW2413013962

What OpenQuestion holds

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LicenceCC BY
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.