Oesophageal adenocarcinoma: A paradigm of mechanical carcinogenesis?
Incidence of adenocarcinoma of the oesophagus and gastric cardia is increasing in most developed countries and strongly associated with obesity and male gender. An underlying increase in the prevalence of gastro-oesophageal reflux has generally been postulated. We suggest that the increase in frequency of reflux and the 2 associated forms of cancer can be explained by growing abdominal pressure brought about by increasing central obesity, most common among men, and sedentary lifestyle, including car use. Abdominal pressure is further accentuated mainly in men by the shift in Western male dressing towards the general use of belts. © 2002 Wiley-Liss, Inc.
A rising incidence of adenocarcinoma of the oesophagus and gastric cardia, mostly in males, has been reported for most developed countries.1, 2, 3, 4, 5 These forms of cancer have been linked to gastro-oesophageal reflux in several studies.6, 7, 8, 9, 10, 11 In addition to male gender, obesity has emerged as a major risk factor.12, 13, 14
The alarming increase in the incidence of adenocarcinoma of the oesophagus and gastric cardia has triggered many studies focused on antiulcer drugs that were gradually introduced during the last 25 years, including H2 receptor antagonists and proton pump inhibitors. These studies have been reviewed,15 and no incriminating evidence against any of these drugs has emerged. In the absence of such evidence, an explanation for the increasing trend of adenocarcinoma of the oesophagus and gastric cardia should accommodate the 3 salient risk factors for this disease: obesity, male gender and the sharply increasing incidence in developed countries (with the exception of some central and western European registries)16, 17, 18 rather than in developing ones,1, 2, 3, 4, 5 though data from the latter are limited.5
We postulate that the increasing frequency over time of gastro-oesophageal reflux and adenocarcinomas of the oesophagus and gastric cardia is due to growing abdominal pressure brought about by obesity, the sitting position and the constraining influence of tight belts. The mechanisms by which obesity increases the risk of oesophageal adenocarcinoma remain open for discussion but may be linked to the predisposition of obese individuals to gastro-oesophageal reflux, hiatal hernia and consequent Barrett's oesophagus.7, 8, 9, 10, 11, 18, 19 Obesity has increased in most developed countries and is gradually affecting developing countries as well. Central obesity, the type of obesity likely to be involved in the postulated pathogenic process, is particularly common among men, though no adequate information is available on type of obesity and oesophageal adenocarcinoma risk. The sitting position characterises sedentary occupations as well as car transportation, both features that tend to increase with time and to be more frequent in economically developed countries. Lastly, belts, particularly among overweight men, have a constraining influence that did not exist in the past, when suspenders were in use.
TESTING OF THE HYPOTHESIS
According to the prevailing popperian view,20 a hypothesis can only be refuted or challenged, rather than empirically confirmed. There are several ways to challenge the proposed hypothesis. It is possible to investigate whether central or peripheral obesity is more important as a risk factor for adenocarcinoma of the oesophagus and gastric cardia: if, controlling for gender, peripheral obesity is more important, the hypothesis would lose much of its credibility. It is also possible to examine time-weighted patterns of sitting rather than standing with emphasis on occupational activity: if, controlling for gender, socioeconomic status and obesity, sedentary occupations were not to emerge as risk factors, the likelihood of the hypothesis being valid would be reduced. Other items of potential value would be time spent sitting in a car, use of suspenders rather than belts, difference in waist circumference before and after undressing (a measure of external pressure to the abdomen) and other related information.
We propose a simple and testable hypothesis to explain the increasing secular trend of adenocarcinoma of the oesophagus and gastric cardia, mostly in developed countries and particularly among overweight men. The hypothesis is unusual in that it implicates mechanical factors rather than chemical, biologic or ionising agents in the carcinogenic process.