Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.

Adenocarcinoma / epidemiology Barrett Esophagus / epidemiology Biomarkers, Tumor / genetics Case-Control Studies Esophageal Neoplasms / epidemiology Eye Proteins / genetics Female Gastroesophageal Reflux / epidemiology Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Obesity / epidemiology Polymorphism, Single Nucleotide RNA-Binding Proteins / genetics Risk Assessment Risk Factors Serine Endopeptidases / genetics Sex Factors
Barrett’s esophagus Genome-Wide Association Study Interaction Sex Difference

Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
12 2020
Historique:
received: 03 05 2020
revised: 04 08 2020
accepted: 24 08 2020
pubmed: 13 9 2020
medline: 16 4 2021
entrez: 12 9 2020
Statut: ppublish

Résumé

Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored. Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits. We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, P The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.

Sections du résumé

BACKGROUND & AIMS
Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored.
METHODS
Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits.
RESULTS
We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, P
CONCLUSIONS
The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.

Identifiants

DOI: 10.1053/j.gastro.2020.08.052 PMID: 32918910 PMC: PMC9057456
pubmed: 32918910
pii: S0016-5085(20)35130-1
doi: 10.1053/j.gastro.2020.08.052
pmc: PMC9057456
mid: NIHMS1627421
pii:
doi:

Substances chimiques

Biomarkers, Tumor 0
Eye Proteins 0
KHDRBS2 protein, human 0
Prss55 protein, human 0
RNA-Binding Proteins 0
RP1L1 protein, human 0
Serine Endopeptidases EC 3.4.21.-

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

2065-2076.e1

Subventions

Organisme : NCI NIH HHS
ID : K05 CA124911
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK034987
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK063616
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA091955
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136725
Pays : United States
Organisme : NIDDK NIH HHS
ID : R21 DK077742
Pays : United States

Investigateurs

Jing Dong (J)
Carlo Maj (C)
Spiridon Tsavachidis (S)
Quinn T Ostrom (QT)
Puya Gharahkhani (P)
Lesley A Anderson (LA)
Anna H Wu (AH)
Weimin Ye (W)
Leslie Bernstein (L)
Oleg Borisov (O)
Julia Schröder (J)
Wong-Ho Chow (WH)
Marilie D Gammon (MD)
Geoffrey Liu (G)
Carlos Caldas (C)
Paul D Pharoah (PD)
Harvey A Risch (HA)
Andrea May (A)
Christian Gerges (C)
Mario Anders (M)
Marino Venerito (M)
Thomas Schmidt (T)
Jakob R Izbicki (JR)
Arnulf H Hölscher (AH)
Brigitte Schumacher (B)
Yogesh Vashist (Y)
Horst Neuhaus (H)
Thomas Rösch (T)
Michael Knapp (M)
Peter Krawitz (P)
Anne Böhmer (A)
Prasad G Iyer (PG)
Brian J Reid (BJ)
Jesper Lagergren (J)
Nicholas J Shaheen (NJ)
Douglas A Corley (DA)
Ines Gockel (I)
Rebecca C Fitzgerald (RC)
Michael B Cook (MB)
David C Whiteman (DC)
Thomas L Vaughan (TL)
Johannes Schumacher (J)
Aaron P Thrift (AP)

Informations de copyright

Copyright © 2020 AGA Institute. All rights reserved.

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Auteurs

Jing Dong (J)

Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas; Division of Hematology and Oncology, Department of Medicine, Cancer Center, and Genomic Sciences & Precision Medicine Center, Medical College of Wisconsin, Milwaukee, Wisconsin.

Carlo Maj (C)

Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Germany.

Spiridon Tsavachidis (S)

Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.

Quinn T Ostrom (QT)

Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.

Puya Gharahkhani (P)

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

Lesley A Anderson (LA)

Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland & Aberdeen Center for Health Data Science, University of Aberdeen, Scotland.

Anna H Wu (AH)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

Weimin Ye (W)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Leslie Bernstein (L)

Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California.

Oleg Borisov (O)

Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Germany.

Julia Schröder (J)

Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Wong-Ho Chow (WH)

Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas.

Marilie D Gammon (MD)

Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina.

Geoffrey Liu (G)

Pharmacogenomic Epidemiology, Ontario Cancer Institute, Toronto, Ontario, Canada.

Carlos Caldas (C)

Cancer Research UK, Cambridge Institute, Cambridge, UK.

Paul D Pharoah (PD)

Department of Oncology, University of Cambridge, Cambridge, UK; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Harvey A Risch (HA)

Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.

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 Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Klinikum, Berlin, Germany.

Marino Venerito (M)

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.

Thomas Schmidt (T)

Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, 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.

Brigitte Schumacher (B)

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

Yogesh Vashist (Y)

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

Michael Knapp (M)

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

Peter Krawitz (P)

Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Germany.

Anne Böhmer (A)

Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Prasad G Iyer (PG)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Brian J Reid (BJ)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Jesper Lagergren (J)

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.

Nicholas J Shaheen (NJ)

Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.

Douglas A Corley (DA)

Division of Research, Kaiser Permanente Northern California, Oakland, California; San Francisco Medical Center, Kaiser Permanente Northern California, San Francisco, California.

Ines Gockel (I)

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

Rebecca C Fitzgerald (RC)

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

Michael B Cook (MB)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

David C Whiteman (DC)

Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

Thomas L Vaughan (TL)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Johannes Schumacher (J)

Center for Human Genetics, University Hospital of Marburg, Marburg, 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. Electronic address: aaron.thrift@bcm.edu.

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Classifications MeSH

questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Carcinomes › Adénocarcinome › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies de l'oesophage › Oesophage de Barrett › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Tumeurs gastro-intestinales › Tumeurs de l'oesophage › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de l'oeil › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies de l'oesophage › Dyskinésies oesophagiennes › Reflux gastro-oesophagien › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Sex-Specific Genetic Associations for...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Appréciation des risques › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › Sex-Specific Genetic Associations for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Facteurs épidémiologiques › Facteurs sexuels › Sex-Specific Genetic Associations for...