Combined effects of obesity, acid reflux and smoking on the risk of adenocarcinomas of the oesophagus

Abstract

Objective: To measure the relative risks of adenocarcinomas of the oesophagus and gastro-oesophageal junction associated with measures of obesity, and their interactions with age, sex, gastro-oesophageal reflux symptoms and smoking. Design and setting: Population-based case-control study in Australia. Patients: Patients with adenocarcinomas of the oesophagus (n = 367) or gastro-oesophageal junction (n = 426) were compared with control participants (n = 1580) sampled from a population register. Main outcome measure: Relative risk of adenocarcinoma of the oesophagus or gastro-oesophageal junction. Results: Risks of oesophageal adenocarcinoma increased monotonically with body mass index (BMI) (p trend ,0.001). Highest risks were seen for BMI >40 kg/m 2 (odds ratio (OR) = 6.1, 95% CI 2.7 to 13.6) compared with ''healthy'' BMI (18.5-24.9 kg/m 2 ). Adjustment for gastro-oesophageal reflux and other factors modestly attenuated risks. Risks associated with obesity were substantially higher among men (OR = 2.6, 95% CI 1.8 to 3.9) than women (OR = 1.4, 95% CI 0.5 to 3.5), and among those aged ,50 years (OR = 7.5, 95% CI 1.7 to 33.0) than those aged >50 years (OR = 2.2, 95% CI 1.5 to 3.1). Obese people with frequent symptoms of gastrooesophageal reflux had significantly higher risks (OR = 16.5, 95% CI 8.9 to 30.6) than people with obesity but no reflux (OR = 2.2, 95% CI 1.1 to 4.3) or reflux but no obesity (OR = 5.6, 95% 2.8 to 11.3), consistent with a synergistic interaction between these factors. Similar associations, but of smaller magnitude, were seen for gastro-oesophageal junction adenocarcinomas. Conclusions: Obesity increases the risk of oesophageal adenocarcinoma independently of other factors, particularly among men. From a clinical perspective, these data suggest that patients with obesity and frequent symptoms of gastro-oesophageal reflux are at especially increased risk of adenocarcinoma.

Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

“…The role of ADH7 in steroid and fat metabolism is also interesting in this disease because of the association with diet, overweight and obesity. 4 We confirm the previously reported reduced expression for the genes PAI-2 (plasminogen activator inhibitor type-2), 37,38 GSTP1 (glutathione S-transferase pi), 39 RB1 (retinoblastoma) 40 and PITX1 (pituitary homeobox 1). 9,24 Of note, PAI-2 expression was more than 100 times lower in EAC than normal esophagus.…”

“…The EAC specimens (all pretreatment) were obtained either from patients at St. Vincent's Hospital or from patients who had been enrolled in the population-based case-control Australian Cancer Study through the Queensland Institute of Medical Research (QIMR). 4 A total of 54 FFPE tissues from 40 patients were studied. Of these, 22 were EAC, 20 IM without dysplasia (BE), and 12 were normal squamous esophagus (NE) biopsies, of which 5 were normal esophagus from patients with no history of BE, EAC or symptoms of gastroesophageal reflux disease and 7 were normal esophagus from patients with BE.…”

Reproducibility of food and nutrient intake estimates using a semi-quantitative FFQ in Australian adults

“…Control subjects were randomly sampled from the Commonwealth Electoral Roll (enrolment is compulsory in Australia and estimated to be 97 % complete) to match the age, sex and geographic distribution of the cases. The method of selection of cases and control subjects has been described in full elsewhere (8,9) . The present study was restricted to control subjects who completed their initial FFQ (FFQ1) during the first few months of the main study (November 2003 to April 2004.…”

Foveolar type dysplasia in Barrett esophagus

“…33 Eight (8) cases of esophageal squamous cell carcinoma were excluded, leaving seventy-three (73) cases (invasive adenocarcinoma n ¼ 68, high-grade dysplasia n ¼ 5).…”