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No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study. Clin Gastroenterol Hepatol 2019 Oct;17(11):2227-2235.e1

Date

02/05/2019

Pubmed ID

30716477

Pubmed Central ID

PMC6675666

DOI

10.1016/j.cgh.2019.01.041

Scopus ID

2-s2.0-85072301158 (requires institutional sign-in at Scopus site)   15 Citations

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.

Author List

Dong J, Gharahkhani P, Chow WH, Gammon MD, Liu G, Caldas C, Wu AH, Ye W, Onstad L, Anderson LA, Bernstein L, Pharoah PD, Risch HA, Corley DA, Fitzgerald RC, Stomach and Esophageal Cancer Study Consortium, Iyer PG, Reid BJ, Lagergren J, Shaheen NJ, Vaughan TL, MacGregor S, Love S, Palles C, Tomlinson I, Gockel I, May A, Gerges C, Anders M, Böhmer AC, Becker J, Kreuser N, Thieme R, Noder T, Venerito M, Veits L, Schmidt T, Schmidt C, Izbicki JR, Hölscher AH, Lang H, Lorenz D, Schumacher B, Mayershofer R, Vashist Y, Ott K, Vieth M, Weismüller J, Nöthen MM, Moebus S, Knapp M, Peters WHM, Neuhaus H, Rösch T, Ell C, Jankowski J, Schumacher J, Neale RE, Whiteman DC, Thrift AP

Author

Jing Dong PhD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Barrett Esophagus
Biomarkers, Tumor
DNA, Neoplasm
Esophageal Neoplasms
Europe
Female
Humans
Male
Mendelian Randomization Analysis
Morbidity
North America
Polymorphism, Single Nucleotide
Risk Assessment
Risk Factors
Vitamin D