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

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% Cl 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% Cl 1.8 to 3.9) than women (OR = 1.4, 95% Cl 0.5 to 3.5), and among those aged <50 years (OR = 7.5, 95% Cl 1.7 to 33.0) than those aged >= 50 years (OR = 2.2, 95% Cl 1.5 to 3.1). Obese people with frequent symptoms of gastro-oesophageal reflux had significantly higher risks (OR = 16.5, 95% Cl 8.9 to 30.6) than people with obesity but no reflux (OR = 2.2, 95% Cl 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.