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Cancer Epidemiol Biomarkers Prev. 2019 Nov 20. doi: 10.1158/1055-9965.EPI-19-0374. [Epub ahead of print]

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

Author information

1
Institute of Human Genetics, University of Bonn, Bonn, Germany. aboehmer@uni-bonn.de.
2
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
3
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
4
Institute of Human Genetics, University of Bonn, Bonn, Germany.
5
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
6
Department of Medicine II, Sana Klinikum, Offenbach, Germany.
7
Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.
8
Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
9
Department of Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Klinikum, Berlin, Germany.
10
Center for Human Genetics, University Hospital Marburg, Marburg, Germany.
11
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
12
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
13
Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
14
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
15
Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
16
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
17
Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
18
Department of General, Visceral and Thoracic Surgery, Klinikum Darmstadt, Darmstadt, Germany.
19
Department of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.
20
Gastroenterologie am Burgweiher, Bonn, Germany.
21
Kantonsspital Aarau, Aarau, Switzerland.
22
Department of General, Visceral and Thorax Surgery, RoMed Klinikum Rosenheim, Rosenheim, Germany.
23
Gastroenterologische Gemeinschaftspraxis, Koblenz, Germany.
24
Centre of Urban Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, University of Essen, Essen, Germany.
25
Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany.
26
Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
27
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
28
University of Central Lancashire, Westlakes Science and Technology Park, Moor Row, United Kingdom.
29
Warwick Medical School, University of Warwick, Warwick, United Kingdom.
30
Medical Research Council (MRC) Cancer Unit, Hutchison-MRC Research Centre and University of Cambridge, Cambridge, United Kingdom.
31
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
32
Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
33
Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas.
#
Contributed equally

Abstract

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 (rg = 0.13, P = 2 × 10-04) and a rg of 0.12 between WHR and BE/EA (P = 1 × 10-02). Sex-specific analyses revealed a pronounced genetic correlation between BMI and EA in females (rg = 0.17, P = 1.2 × 10-03), and WHR and EA in males (rg = 0.18, P = 1.51 × 10-02). On the single marker level, significant enrichment of concordant effects was observed for BMI and BE/EA risk variants (P = 8.45 × 10-03) and WHR and BE/EA risk variants (P = 2 × 10-02).

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.

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