Journal of Gastroenterology

, Volume 37, Supplement 13, pp 10–16 | Cite as

Helicobacter pylori strain-specific modulation of gastric mucosal cellular turnover: implications for carcinogenesis

  • Richard M. Peek


Helicobacter pylori colonization induces inflammation in essentially all hosts, a persistent process that increases the risk of developing distal gastric adenocarcinoma. However, only a small percentage of persons carryingH. pylori develop neoplasia; enhanced risk may be related to differences in expression of specific bacterial products, differences in the host response to the bacteria, or the interaction between host and microbe.H. pylori strains that have thecag pathogenicity island are associated with further increased risk for developing distal gastric cancer; however, host responses toH. pylori, such as altered epithelial cell proliferation and apoptosis, also may be important in lowering the threshold for carcinogenesis.H. pylori cag+ strains selectively enhance proliferation and attenuate apoptosis in human mucosa compared tocag strains. However,cag+ strains also induce more severe gastritis, suggesting that host inflammatory mediators such as cytokines, prostaglandins, and hormones may modulateH. pylori-induced alterations in cellular turnover. In the Mongolian gerbil model of gastric carcinogenesis, apoptosis increases early and transiently followingH. pylori infection, but scores progressively decline despite worsening gastric inflammation. Epithelial cell proliferation peaks later and is significantly related to increased gastrin levels, suggesting that epithelial cell growth inH. pylori-colonized mucosa may be mediated by gastrin-dependent mechanisms. An emerging model invoked by these data is one in whichH. pylori cag+ strains, in conjunction with host mediators, enhance gastric epithelial cell proliferation but not apoptosis in vivo. The combination of increased proliferation without a concordant increase in apoptosis may therefore contribute to the heightened retention of mutagenized cells, which over decades may increase the subsequent risk for gastric cancer.

Key words

apoptosis inflammation cancer gerbils gastrin 


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Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Richard M. Peek
    • 1
    • 2
  1. 1.Division of GastroenterologyVanderbilt University School of MedicineNashvilleUSA
  2. 2.Department of Veterans Affairs Medical CenterNashvilleUSA

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