Shared Genetic Etiology of Obesity-Related Traits and Barrett's Esophagus/Adenocarcinoma: Insights from Genome-Wide Association Studies.

Adenocarcinoma / genetics Barrett Esophagus / genetics Body Mass Index Disease Progression Esophageal Neoplasms / genetics Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Linkage Disequilibrium Male Meta-Analysis as Topic Obesity / genetics Polymorphism, Single Nucleotide Quantitative Trait Loci Risk Assessment Risk Factors Sex Factors Waist-Hip Ratio

Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608

Informations de publication

Date de publication:
02 2020
Historique:
received: 08 04 2019
revised: 09 07 2019
accepted: 15 11 2019
pubmed: 22 11 2019
medline: 20 1 2021
entrez: 22 11 2019
Statut: ppublish

Résumé

Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits. Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses. Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA ( Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mecha-nisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA. Our study quantifies the genetic correlation between BE/EA and obesity. Further research is now warranted to elucidate these effects and to understand the shared pathophysiology.

Sections du résumé

BACKGROUND
Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits.
METHODS
Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses.
RESULTS
Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA (
CONCLUSIONS
Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mecha-nisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA.
IMPACT
Our study quantifies the genetic correlation between BE/EA and obesity. Further research is now warranted to elucidate these effects and to understand the shared pathophysiology.

Identifiants

DOI: 10.1158/1055-9965.EPI-19-0374 PMID: 31748258
pubmed: 31748258
pii: 1055-9965.EPI-19-0374
doi: 10.1158/1055-9965.EPI-19-0374
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

427-433

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH081862
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH087590
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG008976
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089856
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089897
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL120839
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL132825
Pays : United States
Organisme : Medical Research Council
ID : RG84369
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom

Informations de copyright

©2019 American Association for Cancer Research.

Auteurs

Anne C Böhmer (AC)

Institute of Human Genetics, University of Bonn, Bonn, Germany. aboehmer@uni-bonn.de.
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.

Julian Hecker (J)

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Julia Schröder (J)

Institute of Human Genetics, University of Bonn, Bonn, Germany.
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
ORCID: 0000-0002-5278-7904

Puya Gharahkhani (P)

Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Andrea May (A)

Department of Medicine II, Sana Klinikum, Offenbach, Germany.

Christian Gerges (C)

Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.

Mario Anders (M)

Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Department of Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Klinikum, Berlin, Germany.

Jessica Becker (J)

Institute of Human Genetics, University of Bonn, Bonn, Germany.
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.

Timo Hess (T)

Center for Human Genetics, University Hospital Marburg, Marburg, Germany.

Nicole Kreuser (N)

Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.

René Thieme (R)

Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
ORCID: 0000-0002-0537-3979

Tania Noder (T)

Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Marino Venerito (M)

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
ORCID: 0000-0001-8581-0974

Lothar Veits (L)

Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.

Thomas Schmidt (T)

Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
ORCID: 0000-0002-7166-3675

Claudia Fuchs (C)

Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.

Jakob R Izbicki (JR)

Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.

Arnulf H Hölscher (AH)

Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.

Arne Dietrich (A)

Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.

Yusef Moulla (Y)

Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.

Orestis Lyros (O)

Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.

Hauke Lang (H)

Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.

Dietmar Lorenz (D)

Department of General, Visceral and Thoracic Surgery, Klinikum Darmstadt, Darmstadt, Germany.

Brigitte Schumacher (B)

Department of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.

Rupert Mayershofer (R)

Gastroenterologie am Burgweiher, Bonn, Germany.

Yogesh Vashist (Y)

Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
Kantonsspital Aarau, Aarau, Switzerland.

Katja Ott (K)

Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Department of General, Visceral and Thorax Surgery, RoMed Klinikum Rosenheim, Rosenheim, Germany.

Michael Vieth (M)

Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.

Josef Weismüller (J)

Gastroenterologische Gemeinschaftspraxis, Koblenz, Germany.

Susanne Moebus (S)

Centre of Urban Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, University of Essen, Essen, Germany.

Michael Knapp (M)

Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany.

Horst Neuhaus (H)

Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.

Thomas Rösch (T)

Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Christian Ell (C)

Department of Medicine II, Sana Klinikum, Offenbach, Germany.

Markus M Nöthen (MM)

Institute of Human Genetics, University of Bonn, Bonn, Germany.
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.

David C Whiteman (DC)

Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
ORCID: 0000-0003-2563-9559

Ian Tomlinson (I)

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Janusz Jankowski (J)

University of Central Lancashire, Westlakes Science and Technology Park, Moor Row, United Kingdom.
Warwick Medical School, University of Warwick, Warwick, United Kingdom.

Rebecca C Fitzgerald (RC)

Medical Research Council (MRC) Cancer Unit, Hutchison-MRC Research Centre and University of Cambridge, Cambridge, United Kingdom.

Claire Palles (C)

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Thomas L Vaughan (TL)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
ORCID: 0000-0003-1537-0242

Ines Gockel (I)

Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.

Aaron P Thrift (AP)

Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas.
ORCID: 0000-0002-0084-5308

Heide Fier (H)

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Johannes Schumacher (J)

Institute of Human Genetics, University of Bonn, Bonn, Germany.
Center for Human Genetics, University Hospital Marburg, Marburg, Germany.

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Classifications MeSH

questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Carcinomes › Adénocarcinome › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies de l'oesophage › Oesophage de Barrett › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Mesures épidémiologiques › Biométrie › Anthropométrie › Indice de masse corporelle › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Tumeurs gastro-intestinales › Tumeurs de l'oesophage › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Phénomènes génétiques › Liaison génétique › Déséquilibre de liaison › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méta-analyse comme sujet › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › Locus de caractère quantitatif › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Appréciation des risques › Shared Genetic Etiology of Obesity-Related...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Shared Genetic Etiology of Obesity-Related...
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