Helicobacter pylori, duodenal ulcer, gastric cancer: tunnel vision or blinders?

The focus of this paper is on the relationship between Helicobacter pylori gastritis and gastric cancer, one of the most compelling issues after the recent decision of the IARC (International Agency for Research on Cancer) to categorize H. pylori as a carcinogen. Our aim is to identify areas where additional work is not needed and suggest new directions of inquiry. We review what has been accomplished with the advantage of hindsight. Our review of the data regarding current putative virulence factors found that disease and outcome specificity were lacking. The same can be said of the data regarding low gastric juice ascorbate or increased mucosal cell turnover in H. pylori gastritis. We conclude that, while it is certainly possible that some of the factors discovered to date may initiate or mediate certain pathogenetic aspects of H. pylori-related disease, none of them can be seriously proposed as the factor responsible for either gastric cancer or duodenal ulcer. Finally, we identified research areas that might lead to disease-specific associations as well as areas where helicobacters may be used as models for other diseases. We propose that it is time to pause, reflect on what has been done, and focus more sharply on the questions that remain unanswered.