EBioMedicine (Jun 2023)
Dissecting the genetic heterogeneity of gastric cancerResearch in context
- Timo Hess,
- Carlo Maj,
- Jan Gehlen,
- Oleg Borisov,
- Stephan L. Haas,
- Ines Gockel,
- Michael Vieth,
- Guillaume Piessen,
- Hakan Alakus,
- Yogesh Vashist,
- Carina Pereira,
- Michael Knapp,
- Vitalia Schüller,
- Alexander Quaas,
- Heike I. Grabsch,
- Jessica Trautmann,
- Ewa Malecka-Wojciesko,
- Anna Mokrowiecka,
- Jan Speller,
- Andreas Mayr,
- Julia Schröder,
- Axel M. Hillmer,
- Dominik Heider,
- Florian Lordick,
- Ángeles Pérez-Aísa,
- Rafael Campo,
- Jesús Espinel,
- Fernando Geijo,
- Concha Thomson,
- Luis Bujanda,
- Federico Sopeña,
- Ángel Lanas,
- María Pellisé,
- Claudia Pauligk,
- Thorsten Oliver Goetze,
- Carolin Zelck,
- Julian Reingruber,
- Emadeldin Hassanin,
- Peter Elbe,
- Sandra Alsabeah,
- Mats Lindblad,
- Magnus Nilsson,
- Nicole Kreuser,
- René Thieme,
- Francesca Tavano,
- Roberta Pastorino,
- Dario Arzani,
- Roberto Persiani,
- Jin-On Jung,
- Henrik Nienhüser,
- Katja Ott,
- Ralf R. Schumann,
- Oliver Kumpf,
- Susen Burock,
- Volker Arndt,
- Anna Jakubowska,
- Małgorzta Ławniczak,
- Victor Moreno,
- Vicente Martín,
- Manolis Kogevinas,
- Marina Pollán,
- Justyna Dąbrowska,
- Antonio Salas,
- Olivier Cussenot,
- Anne Boland-Auge,
- Delphine Daian,
- Jean-Francois Deleuze,
- Erika Salvi,
- Maris Teder-Laving,
- Gianluca Tomasello,
- Margherita Ratti,
- Chiara Senti,
- Valli De Re,
- Agostino Steffan,
- Arnulf H. Hölscher,
- Katharina Messerle,
- Christiane Josephine Bruns,
- Armands Sīviņš,
- Inga Bogdanova,
- Jurgita Skieceviciene,
- Justina Arstikyte,
- Markus Moehler,
- Hauke Lang,
- Peter P. Grimminger,
- Martin Kruschewski,
- Nikolaos Vassos,
- Claus Schildberg,
- Philipp Lingohr,
- Karsten Ridwelski,
- Hans Lippert,
- Nadine Fricker,
- Peter Krawitz,
- Per Hoffmann,
- Markus M. Nöthen,
- Lothar Veits,
- Jakob R. Izbicki,
- Adrianna Mostowska,
- Federico Martinón-Torres,
- Daniele Cusi,
- Rolf Adolfsson,
- Geraldine Cancel-Tassin,
- Aksana Höblinger,
- Ernst Rodermann,
- Monika Ludwig,
- Gisela Keller,
- Andres Metspalu,
- Hermann Brenner,
- Joerg Heller,
- Markus Neef,
- Michael Schepke,
- Franz Ludwig Dumoulin,
- Lutz Hamann,
- Renato Cannizzaro,
- Michele Ghidini,
- Dominik Plaßmann,
- Michael Geppert,
- Peter Malfertheiner,
- Olivier Gehlen,
- Tomasz Skoczylas,
- Marek Majewski,
- Jan Lubiński,
- Orazio Palmieri,
- Stefania Boccia,
- Anna Latiano,
- Nuria Aragones,
- Thomas Schmidt,
- Mário Dinis-Ribeiro,
- Rui Medeiros,
- Salah-Eddin Al-Batran,
- Mārcis Leja,
- Juozas Kupcinskas,
- María A. García-González,
- Marino Venerito,
- Johannes Schumacher
Affiliations
- Timo Hess
- Institute of Human Genetics, University of Marburg, Marburg, Germany; Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
- Carlo Maj
- Institute of Human Genetics, University of Marburg, Marburg, Germany; Medical Faculty, Institute for Genomic Statistics and Bioinformatics, University of Bonn, Bonn, Germany
- Jan Gehlen
- Institute of Human Genetics, University of Marburg, Marburg, Germany
- Oleg Borisov
- Medical Faculty, Institute for Genomic Statistics and Bioinformatics, University of Bonn, Bonn, Germany
- Stephan L. Haas
- Department of Upper GI Diseases, Karolinska Institutet, Karolinska University Hospital and Unit of Gastroenterology and Rheumatology, Stockholm, Sweden
- Ines Gockel
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany
- Michael Vieth
- Institute for Pathology, Friedrich-Alexander-University Erlangen-Nuernberg, Klinikum Bayreuth, Bayreuth, Germany
- Guillaume Piessen
- Department of Digestive and Oncological Surgery, Claude Huriez Hospital, CHU Lille, Lille, France
- Hakan Alakus
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne, Germany
- Yogesh Vashist
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany; Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
- Carina Pereira
- Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO Porto), Porto 4200-072, Portugal; Porto Comprehensive Cancer Center & RISE @ CI-IPO, University of Porto, Porto 4200-450, Portugal
- Michael Knapp
- Medical Faculty, Institute of Medical Biometrics, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany
- Vitalia Schüller
- Institute of Human Genetics, University of Marburg, Marburg, Germany
- Alexander Quaas
- Medical Faculty, Institute of Pathology, University Hospital Cologne, University of Cologne, Germany
- Heike I. Grabsch
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands; Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom
- Jessica Trautmann
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
- Ewa Malecka-Wojciesko
- Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
- Anna Mokrowiecka
- Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
- Jan Speller
- Medical Faculty, Institute of Medical Biometrics, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany
- Andreas Mayr
- Medical Faculty, Institute of Medical Biometrics, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany
- Julia Schröder
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
- Axel M. Hillmer
- Medical Faculty, Institute of Pathology, University Hospital Cologne, University of Cologne, Germany
- Dominik Heider
- Department of Mathematics and Computer Science, University of Marburg, Marburg, Germany
- Florian Lordick
- University Cancer Center Leipzig, Leipzig University Medical Center, Leipzig, Germany
- Ángeles Pérez-Aísa
- Department of Gastroenterology, Hospital Costa del Sol, Marbella, Spain
- Rafael Campo
- Department of Gastroenterology, Hospital Parc Tauli, Sabadell, Spain
- Jesús Espinel
- Department of Gastroenterology, Complejo Hospitalario, León, Spain
- Fernando Geijo
- Department of Gastroenterology, Hospital Clínico Universitario, Salamanca, Spain
- Concha Thomson
- Department of Gastroenterology, Hospital Obispo Polanco, Teruel, Spain
- Luis Bujanda
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
- Federico Sopeña
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain; Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
- Ángel Lanas
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain
- María Pellisé
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Department of Gastroenterology, Hospital Clinic of Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Claudia Pauligk
- Krankenhaus Nordwest, University Cancer Center, Frankfurt, Germany; Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, Frankfurt, Germany
- Thorsten Oliver Goetze
- Krankenhaus Nordwest, University Cancer Center, Frankfurt, Germany; Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, Frankfurt, Germany
- Carolin Zelck
- Institute of Human Genetics, University of Marburg, Marburg, Germany
- Julian Reingruber
- Institute of Human Genetics, University of Marburg, Marburg, Germany
- Emadeldin Hassanin
- Medical Faculty, Institute for Genomic Statistics and Bioinformatics, University of Bonn, Bonn, Germany
- Peter Elbe
- Department of Upper GI Diseases, Karolinska Institutet, Karolinska University Hospital and Unit of Gastroenterology and Rheumatology, Stockholm, Sweden
- Sandra Alsabeah
- Department of Upper GI Diseases, Karolinska Institutet, Karolinska University Hospital and Unit of Gastroenterology and Rheumatology, Stockholm, Sweden
- Mats Lindblad
- Division of Surgery, Department of Upper GI Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
- Magnus Nilsson
- Division of Surgery, Department of Upper GI Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
- Nicole Kreuser
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany
- René Thieme
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany
- Francesca Tavano
- Gastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
- Roberta Pastorino
- Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
- Dario Arzani
- Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy
- Roberto Persiani
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy; Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
- Jin-On Jung
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Henrik Nienhüser
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Katja Ott
- Department of Surgery, RoMed Klinikum Rosenheim, Rosenheim, Germany
- Ralf R. Schumann
- Institute of Microbiology, Infectious Diseases and Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Oliver Kumpf
- Department of Anaesthesiology and Operative Intensive Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, and Humboldt-Universität zu Berlin, Berlin, Germany
- Susen Burock
- Charité Comprehensive Cancer Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, and Humboldt-Universität zu Berlin, Berlin, Germany
- Volker Arndt
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Anna Jakubowska
- Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Poland; Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University in Szczecin, Poland
- Małgorzta Ławniczak
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Poland
- Victor Moreno
- Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), Hospital Duran I Reynals, Barcelona, Spain; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Faculty of Medicine, Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
- Vicente Martín
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública e CIBERESP), Spain; The Research Group in Gene - Environment and Health Interactions (GIIGAS)/Institute of Biomedicine (IBIOMED), Universidad de Leon, Leon, Spain; Faculty of Health Sciences, Department of Biomedical Sciences, Area of Preventive Medicine and Public Health, Universidad de Leon, Leon, Spain
- Manolis Kogevinas
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública e CIBERESP), Spain; ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Campus Del Mar, Barcelona, Spain; IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Spain
- Marina Pollán
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública e CIBERESP), Spain; Cancer and Environmental Epidemiology Unit, Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain
- Justyna Dąbrowska
- Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland
- Antonio Salas
- Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain; GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), Madrid, Spain
- Olivier Cussenot
- CeRePP, Paris, France; GRC n°5 Predictive Onco-Urology, Tenon Hospital, Sorbonne University, Paris, France
- Anne Boland-Auge
- Centre National de Recherche en Génomique Humaine, CEA, University Paris-Saclay, Evry, France
- Delphine Daian
- Centre National de Recherche en Génomique Humaine, CEA, University Paris-Saclay, Evry, France
- Jean-Francois Deleuze
- Centre National de Recherche en Génomique Humaine, CEA, University Paris-Saclay, Evry, France
- Erika Salvi
- Neuroalgology Unit Fondazione IRCCS, Instituto Neurologico 'Carlo Besta' Milan, Milan, Italy
- Maris Teder-Laving
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
- Gianluca Tomasello
- Medical Oncology Unit, ASST of Cremona, Cremona, Italy; Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Margherita Ratti
- Medical Oncology Unit, ASST of Cremona, Cremona, Italy
- Chiara Senti
- Medical Oncology Unit, ASST of Cremona, Cremona, Italy; Department of Medical Oncology, Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium
- Valli De Re
- Unit of Immunopathologia e Biomarcatori Oncologici/Bio-proteomics Facility, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
- Agostino Steffan
- Unit of Immunopathologia e Biomarcatori Oncologici, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
- Arnulf H. Hölscher
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne, Germany
- Katharina Messerle
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne, Germany
- Christiane Josephine Bruns
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne, Germany
- Armands Sīviņš
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga East University Hospital, Riga, Latvia
- Inga Bogdanova
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga East University Hospital, Riga, Latvia
- Jurgita Skieceviciene
- Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
- Justina Arstikyte
- Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
- Markus Moehler
- Department of Medicine I, University Medical Center of Johannes Gutenberg University Mainz, Mainz, Germany
- Hauke Lang
- Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany
- Peter P. Grimminger
- Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany
- Martin Kruschewski
- Department of General and Visceral Surgery, Klinikum Frankfurt (Oder), Germany
- Nikolaos Vassos
- Division of Surgical Oncology and Thoracic Surgery, Department of Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
- Claus Schildberg
- Department of General Surgery, Brandenburg Medical School Theodor Fontane, University Hospital Brandenburg, Brandenburg, Germany
- Philipp Lingohr
- Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany
- Karsten Ridwelski
- Department of General and Visceral Surgery, Klinikum Magdeburg GmbH, Magdeburg, Germany
- Hans Lippert
- Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke University Hospital, Magdeburg, Germany
- Nadine Fricker
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
- Peter Krawitz
- Medical Faculty, Institute for Genomic Statistics and Bioinformatics, University of Bonn, Bonn, Germany
- Per Hoffmann
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
- Markus M. Nöthen
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
- Lothar Veits
- Institute for Pathology, Friedrich-Alexander-University Erlangen-Nuernberg, Klinikum Bayreuth, Bayreuth, Germany
- Jakob R. Izbicki
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany
- Adrianna Mostowska
- Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland
- Federico Martinón-Torres
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), Madrid, Spain; Department of Pediatrics, Translational Pediatrics and Infectious Diseases Section, Hospital Clínico Universitario de Santiago (SERGAS), Santiago de Compostela, Spain; Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group GENVIP, Instituto de Investigación Sanitaria de Santiago (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
- Daniele Cusi
- Institute of Biomedical Technologies, National Research Council of Italy, Milan, Italy; Bio4Dreams-Business, Nursery for Life Sciences, Milan, Italy
- Rolf Adolfsson
- Department of Clinical Sciences, Umeå University, Umeå, Sweden
- Geraldine Cancel-Tassin
- CeRePP, Paris, France; GRC n°5 Predictive Onco-Urology, Tenon Hospital, Sorbonne University, Paris, France
- Aksana Höblinger
- Department of Internal Medicine I, Community Hospital Mittelrhein, Koblenz, Germany
- Ernst Rodermann
- Association of Medical Practices in Hematology and Internal Oncology, Troisdorf, Germany
- Monika Ludwig
- Association for Oncological Studies (Gefos), Dortmund, Germany
- Gisela Keller
- Institute of Pathology, Technical University of Munich, Munich, Germany
- Andres Metspalu
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Joerg Heller
- Department of Gastroenterology, Marienhaus Hospital Ahrweiler, Ahrweiler, Germany
- Markus Neef
- Department of Gastroenterology, Helios Hospital Siegburg, Siegburg, Germany
- Michael Schepke
- Department of Gastroenterology, Helios Hospital Siegburg, Siegburg, Germany
- Franz Ludwig Dumoulin
- Department of Gastroenterology, St. Elisabeth Hospital Bonn, Bonn, Germany
- Lutz Hamann
- Institute of Microbiology, Infectious Diseases and Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Renato Cannizzaro
- Unit of Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
- Michele Ghidini
- Medical Oncology Unit, ASST of Cremona, Cremona, Italy; Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Dominik Plaßmann
- Gastroenterological Centre, Dr. Plaßmann, Bonn, Germany
- Michael Geppert
- Gastroenterological Centre, Dr. Geppert, Bayreuth, Germany
- Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany; Department of Internal Medicine II, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany
- Olivier Gehlen
- Department of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France
- Tomasz Skoczylas
- 2nd Department of General Surgery, Medical University of Lublin, Lublin, Poland
- Marek Majewski
- 2nd Department of General Surgery, Medical University of Lublin, Lublin, Poland
- Jan Lubiński
- Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Poland
- Orazio Palmieri
- Gastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
- Stefania Boccia
- Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy
- Anna Latiano
- Gastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
- Nuria Aragones
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública e CIBERESP), Spain; Epidemiology Section, Public Health Division, Department of Health of Madrid, Madrid, Spain
- Thomas Schmidt
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Mário Dinis-Ribeiro
- Porto Comprehensive Cancer Center & RISE @ CI-IPO, University of Porto, Porto 4200-450, Portugal; Gastroenterology Department, Portuguese Institute of Oncology of Porto, Porto 4200-072, Portugal
- Rui Medeiros
- Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO Porto), Porto 4200-072, Portugal; Research Department of the Portuguese League Against Cancer-North (LPCC-NRNorte), Porto 4200-177, Portugal
- Salah-Eddin Al-Batran
- Krankenhaus Nordwest, University Cancer Center, Frankfurt, Germany; Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, Frankfurt, Germany
- Mārcis Leja
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga East University Hospital, Riga, Latvia; Digestive Diseases Centre GASTRO, Riga, Latvia
- Juozas Kupcinskas
- Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
- María A. García-González
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain; Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain
- Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
- Johannes Schumacher
- Institute of Human Genetics, University of Marburg, Marburg, Germany; Corresponding author. Center for Human Genetics, University Hospital of Marburg, Baldingerstraße, Marburg 35033, Germany.
- Journal volume & issue
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Vol. 92
p. 104616
Abstract
Summary: Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett’s oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. Funding: German Research Foundation (DFG).
