Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Clin Gastroenterol Hepatol. 2019 Oct;17(11):2227-2235.e1. doi: 10.1016/j.cgh.2019.01.041. Epub 2019 Feb 1.
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).
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.
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).
In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.
循环 25 羟基维生素 D（25（OH）D）浓度的流行病学研究与食管腺癌（EAC）风险之间的关系产生了相互矛盾的结果。我们进行了一项孟德尔随机化研究，以确定循环 25（OH）D 浓度与 EAC 及其前体 Barrett 食管（BE）风险之间的关联。
我们使用两样本（汇总数据）方法进行了一项孟德尔随机化研究。使用与循环 25（OH）D 浓度相关的六个单核苷酸多态性（SNP；rs3755967、rs10741657、rs12785878、rs10745742、rs8018720 和 rs17216707）作为工具变量。我们收集了来自参与 Barrett 和食管腺癌联盟的 6167 名 BE 患者、4112 名 EAC 患者和 17159 名无 BE 或 EAC（对照）的个体的数据，以及来自德国波恩、英国剑桥和牛津的研究数据。分别对 BE 和 EAC 进行了分析。
总体而言，我们没有发现遗传估计的 25（OH）D 浓度与 BE 或 EAC 风险之间存在关联的证据。通过使用逆方差加权法对个体 SNP 关联进行组合来估计 BE 风险时，遗传估计的 25（OH）D 浓度每增加 20 nmol/L，比值比为 1.21（95%CI，0.77-1.92；P=0.41）。通过使用逆方差加权法对个体 SNP 关联进行组合来估计 EAC 风险时，比值比为 0.68（95%CI，0.39-1.19；P=0.18）。
在孟德尔随机化研究中，我们发现低遗传估计的 25（OH）D 浓度与 BE 或 EAC 风险无关。
