Gastric Cancer and Helicobacter pylori: A Critical Evaluation of the Epidemiological Evidence

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Abstract
Despite a dramatic reduction in incidence and mortality, gastric cancer (GC) still was recently reported to be the second most common neoplastic cause of death worldwide. GC treatment has not been improved substantially, and large‐scale early diagnosis programs have not proved feasible outside Japan. On the other hand, even if diet has been shown to play a relevant role in the etiology of GC, primary prevention programs based on dietary modifications are difficult to implement, and results of human chemoprevention trials, although encouraging, have not been confirmed. Overall, the observed reduction in GC risk can reasonably be considered to be the result of a spontaneous trend, somehow related to the widespread improvements in socioeconomic conditions. Domestic refrigeration, an increased availability of fresh fruit and vegetables, and a reduced use of salt are considered to be the most relevant factors in explaining the decreasing temporal trend and the geographical patterns of GC. Recently, evidence of an association between Helicobacter pylori infection and GC has been provided by epidemiological studies, particularly three studies specifically designed as nested case‐control studies in which blood samples were collected well before diagnosis was made. The results of these studies, however, have been confirmed only in part. A strong direct association is not yet widely accepted, and no specific carcinogenic compound or mechanism has been identified. Relevant aspects of GC and H. pylori epidemiology actually do not fit perfectly in a causal hypothesis (i.e., the geographical and gender distribution, the paradoxical association with duodenal ulcer) though, on the other hand, several other factors certainly play a role in the complex multifactorial process leading, over several decades, to GC. Studies focused on H. pylori eradication and its effects on lesions that predispose to GC (atrophic gastritis and metaplasia), however, represent a priority for research, in view of the potential preventive applications. This issue remains controversial, and it is possible that progression of these lesions might occur after eradication.