Helicobacter pylori and gastric cancer.
The International Agency for Research on Cancer, sponsored by the World Health Organization, has recently categorized Helicobacter pylori infection as a class I carcinogen, based on evidence that this infection increases the risk of gastric cancer. The classification was intentionally qualitative in nature and not associated with any public health recommendations. In addition, no specific causal mechanism was proposed to explain the relationship between H. pylori and gastric cancer. In this paper, the magnitude of the risk, implications of the relationship for the prevention of gastric cancer and nature of the causal mechanisms are considered. Relative risk of gastric cancer may be substantial; even with conservative assumptions, the proportion of new cases of gastric cancer worldwide attributable to H. pylori infection is approximately one third of a million annually. This figure is likely to increase with changes in the age structure of the population, and the eradication of H. pylori as a means of prevention of gastric cancer should be considered. A strategy of screening populations in middle age and treating those infected could be relatively inexpensive to administer, but the efficacy is totally unknown and requires evaluation in a randomized controlled trial. Studies designed to address this issue in the general population would need to be large and long-term if gastric cancer is used as an end-point. With respect to carcinogenic mechanisms, a number of constitutive properties of H. pylori may be of relevance to cancer without being specifically carcinogenic. Thus ammonia, which is produced in abundance as a result of urease activity, may promote cell division. Other relevant properties result from the immune response of the host to the bacterium. For example, the excessive production of reactive oxygen metabolites can lead to extensive DNA damage and molecular mutations.
Forman
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Centre for Cancer Research, University of Leeds, Cookridge Hospital, UK.
D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy / Q000453:epidemiology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000382:microbiology* / Q000517:prevention & control