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 language | English (US) |
|---|---|
| Pages (from-to) | 2227-2235.e1 |
| Journal | Clinical Gastroenterology and Hepatology |
| Volume | 17 |
| Issue number | 11 |
| DOIs | |
| State | Published - Oct 2019 |
Fingerprint
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 journal › Article
}
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 -