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

David C. Whiteman ^1*, Shahram Sadeghi ², Nirmala Pandeya ², Bernard Mark Smithers ³, David C Gotley ³, Christopher J Bain ³, Penelope M Webb ¹ and Adele C Green ¹

¹ Queensland Institute of Medical Research, Australia
² University of Queensland, QIMR, Australia
³ University of Queensland, Australia

^* To whom correspondence should be addressed. E-mail: david.whiteman{at}qimr.edu.au.

Accepted 7 August 2007

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 sampled from a population register (n=1,580).

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) (ptrend <0.001). Highest risks were observed for BMI >40 kg/m2 (OR 6.1, 95%CI 2.7-13.6) compared with "healthy" BMI (18.5-24.9 kg/m2). Adjustment for gastro-oesophageal reflux and other factors modestly attenuated risks. Risks associated with obesity were substantially higher among males (OR 2.6, 95%CI 1.8-3.9) than females (OR 1.4, 95% CI 0.5-3.5), and among those <50 years (OR 7.5, 95%CI 1.7-33.0) than >50 years (OR 2.2, 95% CI 1.5-3.1). Obese people with frequent symptoms of gastro-oesophageal reflux had significantly higher risks (OR 16.5, 95% CI 8.9-30.6) than people with obesity but no reflux (OR 2.2, 95%CI 1.1-4.3) or reflux but no obesity (OR 5.6, 95% 2.8-11.3), consistent with a synergistic interaction between these factors. Similar associations, but of lower magnitude, were observed for gastro-oesophageal junction adenocarcinomas.

Conclusions: Obesity increases the risk of oesophageal adenocarcinoma independently of other factors, particularly among males. From a clinical perspective, these data suggest that patients with obesity and frequent symptoms of gastro-oesophageal reflux are at especially elevated risk of adenocarcinoma.

Keywords: adenocarcinoma, case-control study, gastro-oesophageal reflux, obesity, oesophagus

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