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Clin Gastroenterol Hepatol. 2019 Feb 1. pii: S1542-3565(19)30088-6. doi: 10.1016/j.cgh.2019.01.041. [Epub ahead of print]

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma-a Mendelian Randomization Study.

Author information

1
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
2
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
3
Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA.
4
Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
5
Pharmacogenomic Epidemiology, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9.
6
Cancer Research UK, Cambridge Institute, Cambridge, UK.
7
Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
8
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
9
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
10
Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland.
11
Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
12
Department of Oncology, University of Cambridge, Cambridge, UK; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
13
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
14
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA; San Francisco Medical Center, Kaiser Permanente Northern California, San Francisco, CA, USA.
15
Medical Research Council (MRC) Cancer Unit, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, UK.
16
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
17
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
18
Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
19
Centre for Statistics in Medicine and Oxford Clinical Trials Research Unit, Oxford, UK.
20
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
21
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
22
Department of Medicine II, Sana Klinikum, Offenbach, Germany.
23
Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.
24
Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Klinikum, Berlin, Germany.
25
Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
26
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany; Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
27
Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
28
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
29
Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
30
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
31
Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
32
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
33
Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
34
Department of General, Visceral and Thoracic Surgery, Klinikum Darmstadt, Darmstadt, Germany.
35
Department of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.
36
Gastroenterologie am Burgweiher, Bonn, Germany.
37
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany; Kantonsspital Aarau, Aarau, Switzerland.
38
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany; Department of General, Visceral and Thorax Surgery, RoMed Klinikum Rosenheim, Rosenheim, Germany.
39
Gastroenterologische Gemeinschaftspraxis, Koblenz, Germany.
40
Centre of Urban Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, University of Essen, Essen, Germany.
41
Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany.
42
Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
43
Institute of Human Genetics, University of Bonn, Bonn, Germany.
44
Royal College of Surgeons in Ireland, Dublin, Ireland.
45
Cancer Aetiology and Prevention, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
46
Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
47
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA; Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. Electronic address: aaron.thrift@bcm.edu.

Abstract

BACKGROUND & AIMS:

Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE).

METHODS:

We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC.

RESULTS:

Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio (OR) per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P=.41). The OR for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P=.18).

CONCLUSIONS:

In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.

KEYWORDS:

BEACON; chemoprevention; esophageal cancer; etiology; risk factors

PMID:
30716477
DOI:
10.1016/j.cgh.2019.01.041

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