1Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
2Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
3Center for Human Genetics, University Hospital of Marburg, Marburg, Germany
4Institute of Medical Biometrics, Informatics and Epidemiology (IMBIE), Medical Faculty, University of Bonn, Bonn, Germany
5Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Bonn, Germany
6Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany
7Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
8Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany
9Department of Gastroenterology, Oncology and Pneumology, Asklepios Paulinen Clinic Wiesbaden, Wiesbaden, Germany
10Department of Internal Medicine II, Evangelisches Krankenhaus Dusseldorf, Dusseldorf, Germany
11Department of Mathematics and Computer Science, University of Marburg, Marburg, Germany
12Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University Hospital Cologne, Cologne, Germany
13Department of Gastroenterology, University of Leipzig, Leipzig, Germany
14University Cancer Center Leipzig (UCCL), Leipzig University Medical Center, Leipzig, Germany
15Department for General and Visceral Surgery, Städt. Klinikum Dresden Friedrichstadt, Dresden, Germany
16Department of Surgery, Technical University of Munich, School of Medicine, Klinikum Rechts der Isar, München, Germany
17Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Dusseldorf, Medical Faculty of Heinrich Heine University Dusseldorf, Dusseldorf, Germany
18Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital Marburg and Philipps University, Marburg, Germany
19Department of Gastroenterology, University Hospital Augsburg, Augsburg, Germany
20Department for General, Visceral and Trauma Surgery, Elisabeth-Krankenhaus-Essen GmbH, Essen, Germany
21Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany
22Department of Internal Medicine and Gastroenterology, Elisabeth Hospital Essen, Essen, Germany
23Medias Klinikum, Burghausen, Germany
24Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
25Institute of Transfusion Medicine, University Hospital of Schleswig-Holstein, Lübeck/Kiel, Germany
26Institute of Pathology, Friedrich-Alexander-Universiät Erlangen-Nürnberg, Klinikum Bayreuth, Bayreuth, Germany
27Gastroenterologische Gemeinschaftspraxis, Koblenz, Germany
28Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
29Medical Clinic II (Gastroenterology, Hepatology, Endocrinology, Diabetology and Infektiology), Klinikum Fulda, University Medicine Marburg—Campus Fulda, Fulda, Germany
30Medical Faculty, Friedrich Schiller University Jena, Jena, Germany
31Center for Inner Medicine II, Klinikum Chemnitz gGmbH, Chemnitz, Germany
32Division of Hematology and Oncology, Department of Medicine, Cancer Center, and Genomic Sciences & Precision Medicine Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
33Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
34Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
35Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
36Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
37Edinburgh Cancer Research Centre, IGMM, University of Edinburgh, Edinburgh, UK
38Cancer Control, Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
39Medical Research Council (MRC) Cancer Unit, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, Cambridgeshire, UK
40Comprehensive Clinical Trials Unit, University College London, London, UK
Correspondence to Prof Dr Johannes Schumacher, Center for Human Genetics, Universitatsklinikum Giessen und Marburg - Standort Marburg, 35055 Marburg, Germany; [email protected]
JS, LC and CM are joint first authors.
IG, CP and JS are joint senior authors.
Received December 05, 2021; Accepted July 07, 2022
Acknowledgments We thank all patients and controls for participating in this study. This research has been conducted using the UK Biobank Resource under Application Numbers 34390 and 35182. AHi, DHe and JoSc received support for this work from the Else Kröner Fresenius Stiftung (EKFS) (grant number 2013_A118) and the German Federal Ministry of Education and Research (BMBF) (grant number 031L0267A). CPa acknowledges startup funding including a PhD stipend from the University of Birmingham. DEl and AFr were supported by the Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 'Precision Medicine in Chronic Inflammation' (EXC2167). The computations described in this paper were performed using the University of Birmingham's BlueBEAR HPC service, which provides a High Performance Computing service to the University's research community.
IG, CP and JS contributed equally.
JS, LC and CM contributed equally.
Collaborators Members of the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) Marilie D Gammon1, Douglas A Corley2,3, Nicholas J Shaheen4, Nigel C Bird5, Laura J Hardie6, Liam J. Murray7, Brian J Reid8,9, Wong-Ho Chow10, Harvey A Risch11, Weimin Ye12, Geoffrey Liu13, Leslie Bernstein14, Prasad Iyer15, Lesley Anderson16, Jesper Lagergren17,18 Rebecca Fitzgerald19, Anna H Wu20, David C Whiteman21, Thomas L Vaughan 1) Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA; 2) Division of Research, Kaiser Permanente Northern California, Oakland, California, USA; 3) San Francisco Medical Center, Kaiser Permanente Northern California, San Francisco, California, USA; 4) Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA; 5) Department of Oncology, Medical School, University of Sheffield, Sheffield, UK; 6) Division of Epidemiology, University of Leeds, Leeds, UK; 7) Centre for Public Health, Queen's University, Belfast, Northern Ireland; 8) Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 9) Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; 10) Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas, USA; 11) Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA; 12) Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; 13) Pharmacogenomic Epidemiology, Ontario Cancer Institute, Toronto, Ontario, Canada; 14) Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California, USA; 15) Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota; 16) Centre for Public Health, Queen's University Belfast, Northern Ireland, UK; 17) Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 18) Division of Cancer Studies, King's College London, United Kingdom; 19) Medical Research Council (MRC) Cancer Unit, Hutchison-MRC Research Centre and University of Cambridge, Cambridge, United Kingdom; 20) Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA; 21) Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. Members of Esophageal Adenocarcinoma Genetics Consortium (EAGLE) Peter Isaacs1, Conrad Beckett2, Sue Cullen3, David Hobday4, Ameet Dhar5, Deepak Kejariwal6, James Shutt7, Ian Sargeant8, Konrad Koss9, Charles Grimley10, Hugh Barr11, Helen Winter12, Andrew Dixon13,Hugh McMurty14, Matthew Johnson15, Haythem Ali16, Sandro Lazon-Miller17, Stuart Paterson18, Ian Beales19, Chris MacDonald20, Matt Rutter21, Alex Moran22, Chris Haig23, Krish Ragunath24, Siba Senapati25, Pradeep Bhandari26, Saj Wajed27, Salma Alam28, Mark Farrent29, Yeng Ang30, Nigel Trudgill31, Mark Smith32, Keith George33, Arvind Ramadas34, Simon Panter35, Vinod Patel36, Laurence Lovat37, Mark Kelly38, Praful Patel39, Stephen Falk40, Chuka Nwokolo41, John deCaestecker42, Subramaniam Ramakrishnan43, Yang Eng44, Sean Kelly45, Art Tucker46, Paul Mullins47, Hans Prenen48, Janusz Jankowski49 1) Blackpool Victoria Hospital, Blackpool, UK; 2) Bradford Royal Infirmary, Bradford, UK; 3) Wycombe General Hospital, High Wycombe, UK; 4) City Hospitals, Sunderland, UK; 5) Countess of Chester Hospital, Chester, UK; 6) University Hospital of North Durham, County Durham, UK; 7) Dorset County Hospital, 8) Lister Hospital; 9) Macclesfield District General Hospital, Macclesfield, UK; 10) Burnley General Hospital; 11) Gloucestershire Royal Hospital, Gloucester, UK; 12) Great Western Hospital, Swindon, UK; 13) Kettering General Hospital, Kettering, UK; 14) Royal Preston Hospital, Preston, UK; 15) Luton; 16) Maidstone Hospital, Maidstone, UK; 17) Milton Keynes Hospital, Milton Keynes, UK; 18) Forth Valley, Larbert, UK; 19) Norfolk and Norwich University Hospital, Colney Ln, Norwich, UK; 20) Cumberland Infirmary, Carlisle, UK; 21) University Hospital of North Tees, Stockton-onTees, Cleveland, UK; 22) North Devon District Hospital, North Devon, UK; 23) Wansbeck General Hospital, Ashington, UK; 24) Queens Medical Centre, Nottingham, UK; 25) Royal Oldham Infirmary, North Manchester General Hospital 26) Queen Alexandra Hospital, Portsmouth, UK; 27) Royal Devon and Exeter Hospital, Exeter, UK; 28) Royal Marsden Hospital, Surrey, UK; 29) Royal United Hospital Bath, Bath, UK; 30) Salford Royal Hospital, Stott Ln, Salford, UK; 31) Sandwell General Hospital Lyndon, UK; 32) Royal Shrewsbury Hospital, Shrewsbury, UK; 33) Torbay Hospital, Torquay, UK; 34) James Cook University Hospital, Middlesbrough, UK; 35) South Tyneside District Hospital, Southshields, UK; 36) Tameside General Hospital, Ashton-under-Lyne, Lancashire, UK; 37) University College London Hospitals NHS foundation trust, London, UK; 38) Wythenshawe Hospital, Manchester, UK; 39) Southampton General Hospital, Southampton, UK; 40) Bristol Haematology and Oncology Centre, Bristol, UK; 41) University Hospital Coventry, Coventry, UK; 42) Leicester Royal Infirmary, Leicester, UK; 43) Warrington Hospital, Warrington, UK; 44) Royal Albert Edward Infirmary, Wigan, 45) York Teaching Hospital, York, North Yorkshire, UK; 46) St Bartholomews Hospital London (Ethics), London, UK; 47) Prince George Hospital British Columbia (Overseas Advisor), Prince George, BC, Canada; 48) University Hospitals Gasthuisberg, Leuven, Belgium (Overseas Advisor), 49) University of Central Lancashire Medical School Preston, Lancashire, UK. Membership of Wellcome Trust Case Control Consortium 2 Management Committee Peter Donnelly (Chair)1,2, Ines Barroso (Deputy Chair)3, Jenefer M Blackwell4, 5, Elvira Bramon6, Matthew A Brown7, Juan P Casas8, Aiden Corvin9, Panos Deloukas3, Audrey Duncanson10, Janusz Jankowski11, Hugh S Markus12, Christopher G Mathew13, Colin NA Palmer14, Robert Plomin15, Anna Rautanen1, Stephen J Sawcer16, Richard C Trembath13, Ananth C Viswanathan17, Nicholas W Wood18 Data and Analysis Group Chris C A Spencer1, Gavin Band1, Céline Bellenguez1, Colin Freeman1, Garrett Hellenthal1, Eleni Giannoulatou1, Matti Pirinen1, Richard Pearson1, Amy Strange1, Zhan Su1, Damjan Vukcevic1, Peter Donnelly1,2 DNA, Genotyping, Data QC and Informatics Group Cordelia Langford3, Sarah E Hunt3, Sarah Edkins3, Rhian Gwilliam3, Hannah Blackburn3, Suzannah J Bumpstead3, Serge Dronov3, Matthew Gillman3, Emma Gray3, Naomi Hammond3, Alagurevathi Jayakumar3, Owen T McCann3, Jennifer Liddle3, Simon C Potter3, Radhi Ravindrarajah3, Michelle Ricketts3, Matthew Waller3, Paul Weston3, Sara Widaa3, Pamela Whittaker3, Ines Barroso3, Panos Deloukas3. Publications Committee Christopher G Mathew (Chair)13, Jenefer M Blackwell4,5, Matthew A Brown7, Aiden Corvin9, Chris C A Spencer1 1) Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK; 2) Department of Statistics, University of Oxford, Oxford OX1 3TG, UK; 3) Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK; 4) Telethon Institute for Child Health Research, 21—Centre for Child Health Research, University of Western Australia, 100 Roberts Road, Subiaco, Western Australia 6008; 5) Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge CB2 0XY, UK; 6) Department of Psychosis Studies, NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London and The South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AF, UK; 7) University of Queensland Diamantina Institute, Brisbane, Queensland, Australia; 8) Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT and Dept Epidemiology and Public Health, University College London WC1E 6BT, UK; 9) Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Eire; 10) Molecular and Physiological Sciences, The Wellcome Trust, London NW1 2BE; 11) Department of Oncology, Old Road Campus, University of Oxford, Oxford OX3 7DQ, UK, Digestive Diseases Centre, Leicester Royal Infirmary, Leicester LE7 7HH, UK and Centre for Digestive Diseases, Queen Mary University of London, London E1 2AD, UK; 12) Clinical Neurosciences, St George's University of London, London SW17 0RE; 13) King's College London Dept Medical and Molecular Genetics, King's Health Partners, Guy's Hospital, London SE1 9RT, UK; 14) Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK; 15) King's College London Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Denmark Hill, London SE5 8AF, UK; 16) University of Cambridge Dept Clinical Neurosciences, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; 17) NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 2PD, UK; 18) Dept Molecular Neuroscience, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Contributors Manuscript (writing first draft): JuSc, LCh, CMa, CPa, JoSc; Study management: JuSc, LCh, CMa, ABö, MNö, IGo, CPa, JoSc; Samples/Phenotypic data acquisition: THe, NKr, MVe, HAl, AMa, CGe, TSc, RTh, DHe, AHi, JRe, OLy, ADi, AHo, MMe, FLo, GSt, MHo, DRe, JKa, MMü, AEb, CFu, CBr, AHö, HLa, PGr, DDa, YVa, SMa, SGö, AFr, DEl, LVe, JWe, JDo, UBe, TRö, HMe, BSc, HNe, CSc, TWi, SWe, SEs, SBa, JDo, JOn, MBu, ATh, TVa, ITo, DWh, RFi, JJa, MVi, PGh, SMa, IGo; Analysis: JuSc, LCh, CMa, JGe, JSp, OBo, AMa, CPa; Administrative work: JuSc, LCh, CMa, CPa, JoSc; Guarantor: JoSc.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
Data availability statement The dataset for BEACON is available in dbGAP and the dataset of the Cambridge cohort is available via EDAM (see supplement). The other datasets analysed during this study are not publicly available due to non-conformity with consent forms but are available from the corresponding author on reasonable request.
Patient consent for publication Not applicable.
Ethics approval This study involves human participants and was approved by Landesärztekammer Rheinland-Pfalz 837.095.11 (7637), Faculty of Medicine, University of Leipzig 307/15-ek, University of Leipzig 204/19-lk. Participants gave informed consent to participate in the study before taking part.
