Patients with Zollinger-Ellison syndrome does not show an increased risk of developing CRC despite prolonged and marked plasma

elevation of all forms of gastrin (56). Several studies demonstrated that serum/plasma gastrin levels were not significantly different between subjects with and without colorectal neoplasia, and thus unlikely to play a significant role in colorectal tumorigenesis (57-61). Inhibitors,research,lifescience,medical It is interesting to note that some studies have demonstrated that CRC tumor cells express gastrins that may function as autocrine growth factors (62-66). In that scenario, gastrin secretion by tumor cells is likely the source of hypergastrinemia observed in CRC patients. In support of this notion, several studies demonstrated a fall in serum/plasma gastrin values

in CRC patients following surgical resections of the tumors (48,67,68). While these data may further support a role of hypergastrinemia Inhibitors,research,lifescience,medical in colorectal tumorigenesis, they argue against a direct association with H. pylori infection. Change in colorectal microflora Gastric acid barrier is an important regulator of the population and composition of the intestinal microflora (69-72). Atrophic gastritis secondary to H. pylori Inhibitors,research,lifescience,medical infection is associated with reduced acid production, which permits a greater number and variety of microbial species to enter and colonize the intestinal tract. It has been proposed that shifts in the composition of colorectal microflora resulted from H. pylori atrophic gastritis

may facilitate selective growth of bacteria such as B. fragilis, E. faecalis, Inhibitors,research,lifescience,medical and others that are linked to the development of CRC (14-16,18-20). Supporting this hypothesis are studies showing an increased CRC risk following gastric surgery for benign peptic ulcer disease (73,74). However, other studies failed to confirm the association between gastrectomy and subsequent CRC development Inhibitors,research,lifescience,medical (75-78). Toxin production There are different H. pylori strains, some of which are more virulent and more carcinogenic than the others. For instance, patients infected with H. pylori organisms that express cagA gene are more likely to develop gastric cancer than those infected with cagA-negative strains (79,80). Shmuely et al. tested Sitaxentan patients with various malignancies for serum antibodies against H. pylori and CagA protein and found that CagA seropositivity was associated with an increased risk not only for gastric adenocarcinoma but also for colonic adenocarcinoma, when compared with CagA-seronegative controls (81). However, as the Protein Tyrosine Kinase inhibitor authors pointed out, the findings should be interpreted with caution because the tests for H. pylori and CagA were performed at the same time of cancer diagnosis, which raised the question about the temporal relationship between the two conditions. The conclusions of the study were drawn under the assumption that H. pylori infection occurred before CRC development, as for gastric adenocarcinoma.