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

Stomach and Esophageal Cancer Study Consortium

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2227-2235.e1
JournalClinical Gastroenterology and Hepatology
Volume17
Issue number11
DOIs
StatePublished - Oct 2019

Fingerprint

Barrett Esophagus
Random Allocation
Vitamin D
Adenocarcinoma
Single Nucleotide Polymorphism
Odds Ratio
Germany
Epidemiology

Keywords

  • BEACON
  • Chemoprevention
  • Esophageal Cancer
  • Etiology
  • Risk Factors

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

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

In: Clinical Gastroenterology and Hepatology, Vol. 17, No. 11, 10.2019, p. 2227-2235.e1.

Research output: Contribution to journalArticle

@article{c8d69c4b4d124718a8e52b06e55746b8,
title = "No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study",
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",
author = "{Stomach and Esophageal Cancer Study Consortium} and Jing Dong and Puya Gharahkhani and Chow, {Wong Ho} and Gammon, {Marilie D.} and Geoffrey Liu and Carlos Caldas and Wu, {Anna H.} and Weimin Ye and Lynn Onstad and Anderson, {Lesley A.} and Leslie Bernstein and Pharoah, {Paul D.} and Risch, {Harvey A.} and Corley, {Douglas A.} and Fitzgerald, {Rebecca C.} and Iyer, {Prasad G.} and Reid, {Brian J.} and Jesper Lagergren and Shaheen, {Nicholas J.} and Vaughan, {Thomas L.} and Stuart MacGregor and Sharon Love and Claire Palles and Ian Tomlinson and Ines Gockel and Andrea May and Christian Gerges and Mario Anders and B{\"o}hmer, {Anne C.} and Jessica Becker and Nicole Kreuser and Rene Thieme and Tania Noder and Marino Venerito and Lothar Veits and Thomas Schmidt and Claudia Schmidt and Izbicki, {Jakob R.} and H{\"o}lscher, {Arnulf H.} and Hauke Lang and Dietmar Lorenz and Brigitte Schumacher and Rupert Mayershofer and Yogesh Vashist and Katja Ott and Michael Vieth and Josef Weism{\"u}ller and N{\"o}then, {Markus M.} and Susanne Moebus and Michael Knapp",
year = "2019",
month = "10",
doi = "10.1016/j.cgh.2019.01.041",
language = "English (US)",
volume = "17",
pages = "2227--2235.e1",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "11",

}

TY - JOUR

T1 - No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma

T2 - A Mendelian Randomization Study

AU - Stomach and Esophageal Cancer Study Consortium

AU - Dong, Jing

AU - Gharahkhani, Puya

AU - Chow, Wong Ho

AU - Gammon, Marilie D.

AU - Liu, Geoffrey

AU - Caldas, Carlos

AU - Wu, Anna H.

AU - Ye, Weimin

AU - Onstad, Lynn

AU - Anderson, Lesley A.

AU - Bernstein, Leslie

AU - Pharoah, Paul D.

AU - Risch, Harvey A.

AU - Corley, Douglas A.

AU - Fitzgerald, Rebecca C.

AU - Iyer, Prasad G.

AU - Reid, Brian J.

AU - Lagergren, Jesper

AU - Shaheen, Nicholas J.

AU - Vaughan, Thomas L.

AU - MacGregor, Stuart

AU - Love, Sharon

AU - Palles, Claire

AU - Tomlinson, Ian

AU - Gockel, Ines

AU - May, Andrea

AU - Gerges, Christian

AU - Anders, Mario

AU - Böhmer, Anne C.

AU - Becker, Jessica

AU - Kreuser, Nicole

AU - Thieme, Rene

AU - Noder, Tania

AU - Venerito, Marino

AU - Veits, Lothar

AU - Schmidt, Thomas

AU - Schmidt, Claudia

AU - Izbicki, Jakob R.

AU - Hölscher, Arnulf H.

AU - Lang, Hauke

AU - Lorenz, Dietmar

AU - Schumacher, Brigitte

AU - Mayershofer, Rupert

AU - Vashist, Yogesh

AU - Ott, Katja

AU - Vieth, Michael

AU - Weismüller, Josef

AU - Nöthen, Markus M.

AU - Moebus, Susanne

AU - Knapp, Michael

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

KW - BEACON

KW - Chemoprevention

KW - Esophageal Cancer

KW - Etiology

KW - Risk Factors

UR - http://www.scopus.com/inward/record.url?scp=85072301158&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072301158&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2019.01.041

DO - 10.1016/j.cgh.2019.01.041

M3 - Article

C2 - 30716477

AN - SCOPUS:85072301158

VL - 17

SP - 2227-2235.e1

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 11

ER -