Helicobacter pylori: a true carcinogen?

Is Helicobacter pylori a true carcinogen? Most carcinogens are physical, chemical or viral agents which give rise to the development of neoplasia by inducing alterations in cellular DNA. Evidence for the carcinogenic potency of such agents is usually based on dose-response curves and animal models and there is often a direct association with (epi-) genetic events. Despite the absence of such data, H. pylori has been designated as a definite cause of human cancer. This designation is largely based on epidemiological evidence. H. pylori is a carcinogen in the sense that infection with this organism induces a persistently inflamed gastric mucosa which is associated with an increased proliferative state and an increased gastric cancer risk. As such, 1-2% of the infected subjects are estimated to develop cancer, with an incidence probably close to nine times higher than that among non-infected subjects. There is a need for additional mechanistic knowledge on this association between chronic epithelial inflammation and carcinogenesis. An additional important question is whether H. pylori eradication may contribute to gastric cancer prevention. As progressive mucosal abnormalities such as atrophy and metaplasia do not regress after such intervention, the major benefit in terms of cancer prevention is likely to be to infected subjects who have not yet developed permanent gastric mucosal damage. This is in agreement with data suggesting that the role of H. pylori may be confined to the initial stages of carcinogenesis.