Central adiposity and risk of Barrett's esophagus.

BACKGROUND AND AIMS: Aside from chronic reflux, the etiology of Barrett's esophagus (BE) remains largely unknown. This case-control study investigated body mass index (BMI), central adiposity, and cigarette smoking and risk of BE. METHODS: Washington residents newly diagnosed with specialized intestinal metaplasia on at least 1 of 4 esophageal biopsy specimens taken at community gastroenterology clinics (cases [n = 193]) were compared with matched population controls (n = 211). Case subgroups included those with any visible columnar epithelium (visible BE) and those with at least 2 cm of columnar epithelium (long-segment BE [LSBE]). Interviewers conducted personal interviews and took anthropometric measurements. RESULTS: All measures of central adiposity were strongly related to BE risk, particularly for LSBE. For the high category of waist-to-hip ratio (WHR), the adjusted odds ratios were 2.4 (95% confidence interval [CI]: 1.4-3.9) for all cases, 2.8 (95% CI: 1.5-5.1) for visible BE, and 4.3 (95% CI: 1.9-9.9) for LSBE. In contrast, the associations with BMI were weaker. When BMI and WHR were modeled simultaneously, the associations with BMI were greatly attenuated, whereas those with WHR remained strong. Further adjustment for frequency of heartburn did not change these results. Cigarette smoking moderately increased risk but with no evidence of a dose-dependent response or increasing strength by case group. CONCLUSIONS: These observations indicate the importance of identifying the mechanisms underlying obesity's role in BE and esophageal adenocarcinoma, and suggest that weight loss might be a fruitful approach to the prevention of these diseases.

Gastric fluid bile concentrations and risk of Barrett's esophagus.

Patients with Barrett's esophagus are at high risk of progression to adenocarcinoma. A growing, but conflicting body of evidence implicates bile reflux as a contributor to Barrett's esophagus. To investigate whether duodenogastric reflux was associated with an increased risk of Barrett's esophagus, a case-control study of incident Barrett's esophagus was performed. Cases (n=72) were identified by new histologically-confirmed diagnosis of specialized intestinal metaplasia (indicative of Barrett's esophagus) following upper endoscopy for refractory gastroesophageal reflux between October 1997 and September 2000. Cases were compared to gastroesophageal reflux patients without specialized intestinal metaplasia (controls; n=72). There was no difference in total bile acid concentrations between cases and controls. Risk of Barrett's esophagus did not significantly vary with increasing concentrations of total or free bile acids, respectively (OR 0.35 (95% CI 0.12, 1.02) and 0.60 (95% CI 0.22, 1.66)). Low gastric fluid pH (toxic range 3-5), was associated with a non-significant increase in the risk of Barrett's esophagus. In conclusion, no significant association between Barrett's esophagus and total or free bile acids in gastric refluxate was found. Patients with low gastric fluid pH (3-5) may represent a subset of patients at high risk of developing Barrett's esophagus.

Mutagen sensitivity and neoplastic progression in patients with Barrett's esophagus: a prospective analysis.

BACKGROUND: Defects in DNA damage recognition and repair have been associated with a wide variety of cancers. We conducted a prospective study to determine whether mutagen sensitivity, as determined by an in vitro assay, was associated with the future development of cancer in patients with Barrett's esophagus, which is associated with increased risk of progression to esophageal adenocarcinoma. METHODS: We measured sensitivity to bleomycin in peripheral blood lymphocytes in a cohort of 220 patients with Barrett's esophagus. We followed these patients for 1,230 person-years (range, 3 months to 10.1 years; median, 6.4 years), using development of cancer and aneuploidy as end points. A subset of these patients was evaluated for inactivation of tumor-suppressor genes CDKN2A/p16 and TP53 [by mutation and loss of heterozygosity (LOH)] in their Barrett's segments at the time of, or before, the bleomycin test, and the patients were stratified by CDKN2A/p16 and TP53 status in an analysis of mutagen sensitivity and progression. RESULTS: Bleomycin-sensitive patients were found to be at significantly greater risk of developing aneuploidy (adjusted hazard ratio, 3.71; 95% confidence interval, 1.44-9.53) and nonsignificantly greater risk of cancer (adjusted hazard ratio, 1.63; 95% confidence interval, 0.71-3.75). Among patients with detectable LOH at the TP53 locus (on chromosome 17p), increasing bleomycin sensitivity was associated with increased risk of developing cancer (P(trend) < 0.001) and aneuploidy (P(trend) = 0.005). CONCLUSIONS: This study supports the hypothesis that sensitivity to mutagens increases the risk of neoplastic progression in persons with Barrett's esophagus, particularly those with 17p LOH including TP53.