Evidence map›Paper›PMID 25447851›Full record

ArticleGastroenterology2015

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

Claire Palles, Laura Chegwidden, Xinzhong Li, John M Findlay, Garry Farnham, Francesc Castro Giner, Maikel P Peppelenbosch, Michal Kovac, Claire L Adams, Hans Prenen and 88 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 7 pooled it
12.6field-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

73 citing papers in PubMed, 7 syntheses or guidelines pooled it, 110 citations in OpenAlex.

  1. Pooled it
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  8. Article
  9. Observational
  10. Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026
    Review
  11. Article
  12. Article
  13. Pathogenesis of Barrett's Esophagus: Evolving and Emerging Mechanisms.Gastrointestinal endoscopy clinics of North America · 2026
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Sleep Behaviors, Genetic Predispositions, and Risk of Esophageal Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2023
    Article
  20. Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

98 authors at 20 institutions in 8 countries.

Claire PallesWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Electronic address: cpalles@well.ox.ac.uk.
Laura ChegwiddenPlymouth University Peninsula School of Medicine and Dentistry, Plymouth, Devon, UK.
Xinzhong LiCentre of Biostatistics, Bioinformatics and Biomarkers, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, Devon, UK.
John M FindlayWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Garry FarnhamPlymouth University Peninsula School of Medicine and Dentistry, Plymouth, Devon, UK.
Francesc Castro GinerWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Maikel P PeppelenboschDepartment of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Michal KovacWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Claire L AdamsPlymouth University Peninsula School of Medicine and Dentistry, Plymouth, Devon, UK.
Hans PrenenDepartment of Digestive Oncology, University Hospital Gasthuisberg, Leuven, Belgium.
Sarah BriggsWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Rebecca HarrisonDepartment of Pathology, Leicester Royal Infirmary, Leicester, UK.
Scott SandersDepartment of Cellular Pathology, Warwick Hospital, Warwick, UK.
David MacDonaldDepartment of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Chris HaighDepartment of Gastroenterology, Wansbeck General Hospital, Ashington, Northumberland, UK.
Art TuckerWilliam Harvey Research Institute, The Ernest Cooke Vascular & Microvascular Unit, Centre for Clinical Pharmacology, St Bartholomew's Hospital, London, UK.
Sharon LoveCentre for Statistics in Medicine and Oxford Clinical Trials Research Unit, Oxford, UK.
Manoj NanjiCentre for Digestive Diseases, Queen Mary University of London, London, UK.
John deCaesteckerDepartment of Gastroenterology, Leicester General Hospital, Leicester, UK.
David FerryDepartment of Oncology, New Cross Hospital, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK.
Barrie RathboneDepartment for Gastroenterology, Leicester Royal Infirmary, Leicester, UK.
Julie HapeshiGloucestershire Royal Hospital, Great Western Road, Gloucester, UK.
Hugh BarrDepartment of Upper GI Surgery, Gloucestershire, Royal Hospital, Gloucester, UK.
Paul MoayyediDepartment of Medicine, McMaster HC, Hamilton Ontario, Canada.
Peter WatsonSchool of Medicine, Dentistry, and Biomedical Sciences, Centre for Public Health, Queens University Belfast, NI.
Barbara ZietekCentre for Digestive Diseases, Queen Mary University of London, London, UK.
Neera MarooCentre for Digestive Diseases, Queen Mary University of London, London, UK.
Laura GayCentre for Digestive Diseases, Queen Mary University of London, London, UK.
Tim UnderwoodUniversity of Southampton, Southampton General Hospital, Tremona Road, Southampton, UK.
Lisa BoulterUniversity of Southampton, Southampton General Hospital, Tremona Road, Southampton, UK.
Hugh McMurtryLancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Lancashire, UK.
David MonkGeneral Surgery, Countess of Chester Hospital, Chester, UK.
Praful PatelSouthampton University Hospitals NHS Trust, Southampton, UK.
Krish RagunathWolfson Digestive Diseases Centre, Queens Medical Centre, Nottingham, UK.
David Al DulaimiWorcestershire Acute Hospitals NHS Trust, Alexandra Hospital, Redditch, UK.
Iain MurrayDepartment of Gastroenterology, Royal Cornwall Hospital, Truro, Cornwall, UK.
Konrad KossMacclesfield General Hospital, Macclefield, Cheshire, UK.
Andrew VeitchDepartment of Oncology, New Cross Hospital, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK.
Nigel TrudgillDepartment of Gastroenterology, Sandwell General Hospital, Lyndon, West Bromwich, UK.
Chuka NwokoloDepartment of Gastroenterology, University Hospital of Coventry, Coventry, UK.
Bjorn RembackenDepartment of Gastroenterology, Leeds General Infirmary, Leeds, UK.
Paul AtherfoldDepartment of Clinical Pharmacology University of Oxford, Oxford, UK.
Elaine GreenSchool of Biomedical & Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.
Yeng AngGastroenterology, Royal Albert Edward Infirmary NHS Trust, Wigan, UK; GI Science Centre, Salford Royal NHS Foundation Trust, University of Manchester, Salford, UK.
Ernst J KuipersDepartment of Gastroenterology and Hepatology, Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Wu ChowForth Valley Royal Hospital, Larbert, Scotland, UK.
Stuart PatersonNorfolk and Norwich University Hospitals NHS Foundation Trust, Norfolk and Norwich University Hospital, Norwich, UK.
Sudarshan KadriDepartment for Gastroenterology, Leicester Royal Infirmary, Leicester, UK.
Ian BealesBurnley General Hospital, Burnley, Lancashire, UK.
Charles GrimleyHead of Gastroenterology, University Hospital of Northern BC, Prince George, British Columbia, Canada.
Paul MullinsBradford Teaching Hospitals NHS Foundation Trust, Bradford Royal Infirmary, Bradford, UK.
Conrad BeckettRoyal United Hospital Bath NHS Trust, Royal United Hospital, Avon, Bath, Somerset, UK.
Mark FarrantKettering General Hospital NHS Foundation Trust, Kettering General Hospital, Rothwell Road, Kettering, Northants, UK.
Andrew DixonYork Teaching Hospital NHS Foundation Trust, York, UK.
Sean KellyLuton and Dunstable University Hospital NHS Foundation Trust, Luton, Bedfordshire, UK.
Matthew JohnsonDepartment of Thoracic and Upper Gastrointestinal Surgery, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Shahjehan WajedCounty and Durham and Darlington NHS Foundation Trust, Bishop Auckland, County Durham, UK.
Anjan DharGuy's and St Thomas' NHS Foundation Trust, London, UK.
Elinor SawyerBarts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
Rebecca RoylanceDivision of Public Health Sciences, Fred Hutchinson Cancer Research Centre, Seattle, Washington.
Lynn OnstadDepartment of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, North Carolina.
Marilie D GammonDivision of Research and San Francisco Medical Center, Kaiser Permanente Northern California, California.
Douglas A CorleyDivision of Gastroenterology and Hepatology, UNC School of Medicine, University of North Carolina, Chapel Hill, North Carolina.
Nicholas J ShaheenDepartment of Oncology, The Medical School, University of Sheffield, UK.
Nigel C BirdDivision of Epidemiology, University of Leeds, Leeds, UK.
Laura J HardieDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Brian J ReidDepartment of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, North Carolina; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Weimin YePrincess Margaret Cancer Centre, Ontario Cancer Institute, Toronto, ON, Canada.
Geoffrey LiuDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Yvonne RomeroRegistry, On behalf of the Romero; Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California.
Leslie BernsteinDepartment of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.
Anna H WuDepartment of Surgery, University of Saskatchewan, Saskatoon, Canada.
Alan G CassonMRC Cancer Cell Unit, Hutchison-MRC Research Centre and University of Cambridge, Cambridge, UK.
Rebecca FitzgeraldCancer Control, QIMR Berghofer Medical Research Institute, Queensland, Australia.
David C WhitemanDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
Harvey A RischDepartment of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
David M LevineDepartment of Gastroenterology, Tergooi Hospital, Hilversum, The Netherlands.
Tom L VaughanDepartment of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, North Carolina.
Auke P VerhaarDepartment of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Jan van den BrandeDepartment of Surgery, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Eelke L ToxopeusDepartment of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
Manon C SpaanderDepartment of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Bas P L WijnhovenDepartment of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
Luc J W van der LaanDepartment of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
Kausilia KrishnadathDepartment of Genetics, University Medical Centre Groningen and University of Groningen, The Netherlands.
Cisca WijmengaDepartment of Clinical Medicine & Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St James's Hospital, Dublin, Ireland.
Gosia TrynkaDepartment of Clinical Medicine & Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St James's Hospital, Dublin, Ireland.
Ross McManusDepartment of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, St. James' Hospital, Dublin, Ireland.
John V ReynoldsGastrointestinal Unit, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland.
Jacintha O'SullivanGastrointestinal Unit, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland.
Padraic MacMathunaFaculty of Medicine, Imperial College London, South Kensington Campus, London, UK.
Sarah A McGarrigleGastrointestinal Unit, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland.
Dermot KelleherFaculty of Medicine, Imperial College, South Kensington Campus, London, UK.
Severine VermeireDepartment of Digestive Oncology, University Hospital Gasthuisberg, Leuven, Belgium.
Isabelle CleynenDepartment of Digestive Oncology, University Hospital Gasthuisberg, Leuven, Belgium.
Raf BisschopsDepartment of Digestive Oncology, University Hospital Gasthuisberg, Leuven, Belgium.
Ian TomlinsonWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Electronic address: iant@well.ox.ac.uk.
Janusz JankowskiUniversity Hospitals Coventry & Warwickshire NHS Trust, Warwickshire, England; Warwick Medical School, University of Warwick, Warwickshire, England. Electronic address: J.Jankowski@warwick.ac.uk.
Queen Mary University of London · GBPeninsula College of Medicine and Dentistry · GBUniversity of Oxford · GBAmsterdam UMC Location University of Amsterdam · NLCentre for Human Genetics · GBErasmus University Rotterdam · NLLeicester Royal Infirmary · GBUniversity College Dublin · IEUniversity of North Carolina at Chapel Hill · USErasmus MC · NLFred Hutch Cancer Center · USGloucestershire Royal Hospital · GBImperial College London · GBTrinity College Dublin · IEAlexandra Hospital · GBBeckman Research InstituteBradford Royal Infirmary · GBBurnley General Teaching Hospital · GBCounty Durham and Darlington NHS Foundation Trust · GBForth Valley Royal Hospital · GB

Funding

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
Non-Endoscopic Surveillance for Barrett's Esophagus Following Ablative TherapyK24DK100548 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHAHEEN, NICHOLAS J · 2013 to 2017
$896k
EPIDEMIOLOGY OF BARRETTS ESOPHAGUSR01CA072866 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI VAUGHAN, THOMAS L · 1997 to 2000
$543k
Cancer Research UK 16895Cancer Research UK 4584Medical Research Council G1002565Medical Research Council MC_PC_14105NCI NIH HHS K05 CA124911NCI NIH HHS P01 CA091955NCI NIH HHS R01 CA072866NCI NIH HHS R01 CA136725NIDDK NIH HHS K24 DK100548Wellcome TrustWellcome Trust 084722/Z/08/ZWellcome Trust 090532/Z/09/Z
6 · The paper itself

Abstract

BACKGROUND &

aimsBarrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.

methodsWe performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.

resultsWe identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)).

conclusionsWe identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

Indexed as

Genetic Predisposition to DiseasePolymorphism, Single NucleotideBarrett EsophagusBone Morphogenetic ProteinsEsophageal NeoplasmsGenome-Wide Association StudyGrowth Differentiation FactorsHumansRiskT-Box Domain ProteinsBone Morphogenetic ProteinsGDF7 protein, humanGrowth Differentiation FactorsT-Box Domain ProteinsT-box transcription factor 5CancerEACIntestinal MetaplasiaSusceptibility

Identifiers

PMID25447851
PMCPMC4315134
OpenAlexW2140102429

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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.