HELICOBACTER PYLORI INFECTION IN GASTRIC CANCEROGENESIS

Gastric cancer (GS) remains one of the most common cancers worldwide. It is considered as the second most frequent cause of cancer death worldwide, although much geographical variation in incidence exists. Many studies before linked Helicobacter pylori (Hp) which is now considered as an important pathogen, to the risk of developing noncardia GS. This overview attempts to summarize the recent basic and clinical evidence on the link between H. pylori and gastric cancer, after the award of the Nobel Prize for Physiology or Medicine to Drs. J.R. Warren and B.J. Marshall for the first culture and isolation of Hp and the investigation of their relevance to peptic ulcer disease. It become evident that Hp eradication by antibiotic treatment combined with proton pump inhibitor (PPI) serves as the primary chemoprevention strategy to reduce gastric cancer incidence. Moreover, the eradication therapy reduces gastric cancer incidence in patients without any precancerous lesions at the baseline and is most effective before the development of atrophic gastritis. Due to understanding the molecular nature of GC which has been nowadays under intense investigation, our review attempts to highlight recent progress in the field of research on Hp-induced GS. We discuss the geographical diversity in Hp infection and cancer incidence and the mechanistic role of gastrin, cyclooxygenase-2 (COX-2), growth factor, nitric oxide (NO)/NO synthase and E-cadherin/beta-cathenin systems, apoptosis and angiogenesis in Hp-induced gastric carcinogenesis. In addition host-related genetic susceptibility and the role of overexpression of a proinflammatory cytokines and their polymorphism is discussed in the relation to the cascade of events such as gastric atrophy, intestinal metaplasia and dysplasia that finally lead to adenocarcinoma.