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Multicenter Study
. 2019 Oct;17(11):2227-2235.e1.
doi: 10.1016/j.cgh.2019.01.041. Epub 2019 Feb 1.

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study

Jing Dong  1 , Puya Gharahkhani  2 , Wong-Ho Chow  3 , Marilie D Gammon  4 , Geoffrey Liu  5 , Carlos Caldas  6 , Anna H Wu  7 , Weimin Ye  8 , Lynn Onstad  9 , Lesley A Anderson  10 , Leslie Bernstein  11 , Paul D Pharoah  12 , Harvey A Risch  13 , Douglas A Corley  14 , Rebecca C Fitzgerald  15 ; Stomach and Esophageal Cancer Study Consortium; Prasad G Iyer  16 , Brian J Reid  9 , Jesper Lagergren  17 , Nicholas J Shaheen  18 , Thomas L Vaughan  9 , Stuart MacGregor  2 , Sharon Love  19 , Claire Palles  20 , Ian Tomlinson  20 , Ines Gockel  21 , Andrea May  22 , Christian Gerges  23 , Mario Anders  24 , Anne C Böhmer  25 , Jessica Becker  26 , Nicole Kreuser  21 , Rene Thieme  21 , Tania Noder  27 , Marino Venerito  28 , Lothar Veits  29 , Thomas Schmidt  30 , Claudia Schmidt  31 , Jakob R Izbicki  32 , Arnulf H Hölscher  31 , Hauke Lang  33 , Dietmar Lorenz  34 , Brigitte Schumacher  35 , Rupert Mayershofer  36 , Yogesh Vashist  37 , Katja Ott  38 , Michael Vieth  29 , Josef Weismüller  39 , Markus M Nöthen  25 , Susanne Moebus  40 , Michael Knapp  41 , Wilbert H M Peters  42 , Horst Neuhaus  43 , Thomas Rösch  23 , Christian Ell  22 , Janusz Jankowski  44 , Johannes Schumacher  25 , Rachel E Neale  45 , David C Whiteman  46 , Aaron P Thrift  47
Affiliations
Multicenter Study

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study

Jing Dong et al. Clin Gastroenterol Hepatol. 2019 Oct.

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 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 odds ratio 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.

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Conflict of interest statement

Conflicts of Interest: The authors disclose no potential conflicts of interest.

Figures

Figure 1A.
Figure 1A.. Mendelian randomization estimates of the association between increased 25(OH)D concentration and risk of Barrett’s esophagus.
The OR estimates are per 20 nmol/L increase in 25(OH)D concentration. The hollow diamond represents the overall IV estimate with its 95% CI.
Figure 1B.
Figure 1B.. Mendelian randomization estimates of the association between increased 25(OH)D concentration and risk of esophageal adenocarcinoma.
The OR estimates are per 20 nmol/L increase in 25(OH)D concentration. The hollow diamond represents the overall IV estimate with its 95% CI.
See this image and copyright information in PMC

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