Risk factors for Barrett’s oesophagus and oesophageal adenocarcinoma:Results from the FINBAR study

AIM:To investigate risk factors associated with Barrett's oesophagus and oesophageal adenocarcinoma.METHODS:This all-Ireland population-based case-control study recruited 224 Barrett's oesophagus patients,227 oesophageal adenocarcinoma patients and 260 controls.All participants underwent a structured interview with information obtained about potential lifestyle and environmental risk factors.RESULTS:Gastro-oesophageal reflux was associated with Barrett's [OR 12.0(95% CI 7.64-18.7)] and oesophageal adenocarcinoma [OR 3.48(95% CI 2.25-5.41)].Oesophageal adenocarcinoma patients were more likely than controls to be ex-or current smokers [OR 1.72(95% CI 1.06-2.81)and OR 4.84(95% CI 2.72-8.61)respectively] and to have a high body mass index [OR 2.69(95% CI 1.62-4.46)].No significant associations were observed between these risk factors and Barrett's oesophagus.Fruit but not vegetables were negatively associated with oesophageal adenocarcinoma [OR 0.50(95% CI 0.30-0.86)].CONCLUSION:A high body mass index,a diet low in fruit and cigarette smoking may be involved in the progression from Barrett's oesophagus to oesophageal adenocarcinoma.

Low circulating levels of gastrin-17 in patients with Barrett's esophagus

AIM: To examine whether the fasting levels of serum gastrin-17 (G-17) are lower in Barrett's esophagus (BE)patients than in non-Barrett controls.METHODS: Nineteen patients with BE (presenting with a tubular segment ≥2 cm long in lower esophagus and intestinal metaplasia of incomplete type ('specialized columnar epithelium') in endoscopic biopsies from the tubular segment below the squamocolumnar junction were collected prospectively from outpatients referred to diagnostic gastroscopy. The controls comprised 199 prospectively collected dyspeptic outpatients without BE or any endoscopically visible lesions in the upper GI tract.Fasting levels of serum G-17 (G-17fast) were assayed with an EIA test using a Mab highly specific to amidated G-17. None of the patients and controls received therapy with PPIs or other antisecretory agents.RESULTS: The mean and median levels of G-17fast in serum were significantly lower (P = 0.001) in BE patients than in controls. The positive likelihood ratios (LR+) of low G-17fast to predict BE in the whole study population at G-17fast levels ＜0.5, ＜1, or ＜1.5 pmol/L were 3.5, 3.0,and 2.8, respectively. Among patients and controls with healthy stomach mucosa, the LR+ were 5.6, 3.8, and 2.6,respectively. In the whole study population, serum G-17 was below 2 pmol/L in 15 of 19 BE patients (79%). The corresponding prevalence was 66 of 199 (33%) in controls (P＜0.001). The G-17fast was 5 pmol/L or more in only one of the 19 BE patients (5%). In controls, 76 of the 199 patients (38%) had such high serum G-17fast levels (P＜0.01).CONCLUSION: Serum levels of G-17fast tend to be lower in native patients with BE than in healthy controls.

Gene expression in rats with Barrett's esophagus and esophageal adenocarcinoma induced by gastroduodenoesophageal reflux

AIM: To study the different gene expression profiles in rats with Barrett's esophagus (BE) and esophageal adenocarcinoma (EA) induced by gastro-duodenoesophageal reflux.METHODS: Esophagoduodenostomy was performed in 8-wk old Sprague-Dawley rats to induce gastro-duodenoesophageal reflux, and a group of rats that received sham operation served as control. Esophageal epithelial pathological tissues were dissected and frozen in liquid nitrogen immediately. The expression profiles of 4 096genes in EA and BE tissues were compared to normal esophagus epithelium in normal control (NC) by cDNA microarray.RESULTS: Four hundred and forty-eight genes in BE were more than three times different from those in NC, including 312 upregulated and 136 downregulated genes. Three hundred and seventy-seven genes in EA were more than three times different from those in NC, including 255upregulated and 142 downregulated genes. Compared to BE, there were 122 upregulated and 156 downregulated genes in EA. In the present study, the interested genes were those involved in carcinogenesis. Among them, the upregulated genes included cathepsin C, aminopeptidase M, arachidonic acid epoxygenase, tryptophan-2,3-dioxygenase, ubiquitin-conjugating enzyme, cyclic GMP-stimulated phosphodiesterase, tissue inhibitor of metalloproteinase-1, betaine-homocysteine methyltransferase, lysozyme, complement 4b binding protein,complement 9 protein, insulin-like growth factor binding protein, UDP-glucuronosyltransferase, tissue inhibitor of metalloproteinase-3, aldolase B, retinoid X receptor gamma, carboxylesterase and testicular cell adhesion molecule 1. The downregulated genes included glutathione synthetase, lecithin-cholesterol acyltransferase, p55CDC,heart fatty acid binding protein, cell adhesion regulator and endothelial cell selectin ligand.CONCLUSION: Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux may develop into BE and even EA gradually. The gene expression level is different between EA and BE, and may be related to the occurrence and progression of EA.