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
N1 - Funding Information:
Funding This work was funded primarily by the National Institutes of Health (R01CA136725). Also supported by a research training grant from the Cancer Prevention and Research Institute of Texas (RP160097 to J.D.); by a grant from the National Health and Medical Research Council of Australia (1123248 to P.G.); by the Alan B. Brown Chair in Molecular Genomics and by the Cancer Care Ontario Chair in Experimental Therapeutics and Population Studies (G.L.). The University of Cambridge received salary support from the National Health Service in the East of England through the Clinical Academic Reserve (P.D.P.). Also supported by a grant (P01CA91955) from the National Institutes of Health/National Cancer Institute (B.J.R.); by a grant (P30 DK034987) from the National Institutes of Health (N.J.S.); by a National Institutes of Health Established Investigator Award (K05CA124911 to T.L.V.); by an Australian Research Council Future Fellowship (S.M.); and by Research Fellowships from the National Health and Medical Research Council of Australia (D.C.W. and R.E.N.). The funders of the study had no role in the design, analysis, or interpretation of the data, or in writing or publication decisions related to this article.
Funding Information:
The authors thank all patients and controls for participating in this study. The MD Anderson controls were drawn from the database of Genotypes and Phenotypes (study accession: phs000187.v1.p1). Genotyping of these controls was performed through the University of Texas MD Anderson Cancer Center and the Johns Hopkins University Center for Inherited Disease Research. The authors acknowledge the principal investigators of that study: Christopher Amos, Qingyi Wei, and Jeffrey E. Lee. Controls from the Genome-Wide Association Study of Parkinson Disease were obtained from the database of Genotypes and Phenotypes (study accession: phs000196.v2.p1). This work, in part, used data from the National Institute of Neurological Disorders and Stroke the database of Genotypes and Phenotypes database from the Center for Inherited Disease Research:NeuroGenetics Research Consortium Parkinson's disease study. The authors acknowledge the principal investigators and co-investigators of that study: Haydeh Payami, John Nutt, Cyrus Zabetian, Stewart Factor, Eric Molho, and Donald Higgins. Controls from the Chronic Renal Insufficiency Cohort were drawn from the database of Genotypes and Phenotypes (study accession: phs000524.v1.p1). The Chronic Renal Insufficiency Cohort study was performed by the Chronic Renal Insufficiency Cohort investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Data and samples from the Chronic Renal Insufficiency Cohort reported here were supplied by National Institute of Diabetes and Digestive and Kidney Diseases Central Repositories. This report was not prepared in collaboration with investigators of the Chronic Renal Insufficiency Cohort study and does not necessarily reflect the opinions or views of the Chronic Renal Insufficiency Cohort study, the National Institute of Diabetes and Digestive and Kidney Diseases Central Repositories, or the National Institute of Diabetes and Digestive and Kidney Diseases. The authors acknowledge the principal investigators and the project officer of that study: Harold I. Feldman, Raymond R. Townsend, Lawrence J. Appel, Mahboob Rahman, Akinlolu Ojo, James P. Lash, Jiang He, Alan S. Go, and John W. Kusek.
Publisher Copyright:
© 2019 AGA Institute
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
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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 -