Gastrin and gastric cancer

Abstract

Gastric cancer although occurring in reduced frequency is still an important disease, partly because of the bad prognosis when occurring in western countries. This decline in occurrence may mainly be due to the reduced prevalence of Helicobacter pylori (Hp) infection, which is the most important cause of gastric cancer. There exist many different pathological classifications of gastric carcinomas, but the most useful seems to be the one by Lauren into intestinal and diffuse types since these types seldom transform into the other and also have different epidemiology. During the nearly 30 years that have passed since the groundbreaking description of Hp as the cause of gastritis and gastric cancer, a continuous search for the mechanism by which Hp infection causes gastric cancer has been done. Interestingly, it is mainly atrophic gastritis of the oxyntic mucosa that predisposes to gastric cancer possibly by inducing hypoacidity and hypergastrinemia. There are many arguments in favor of an important role of gastrin and its target cell, the enterochromaffin-like cell, in gastric carcinogenesis. The role of gastrin in gastric carcinogenesis implies caution in the long-term treatment with inhibitors of gastric acid secretion inducing secondary hypergastrinemia, in a common disease like gastroesophageal reflux disease.Keywords: carcinogenesis, classification of cancer, gastric cancer, gastrin, hormones, neuroendocrine neoplasia Gastric cancer has been one of the most prevalent cancers and combined with a high mortality, gastric cancer has been among the leading causes of cancer death. However, there has been a continuous decline in the prevalence of gastric cancers during the last decades. Unfortunately, in spite of widespread use of upper gastrointestinal endoscopy, the prognosis in patients affected in the western world has not been much improved. This is in contrast to Japan where gastric cancer often is diagnosed at an early phase allowing removal and a better prognosis (1, 2). This is partly due to special screening programs in Japan having a high prevalence of gastric cancer (1, 2), resulting in diagnoses at a curable stage. In most western countries, the prevalence is much lower (3), and therefore, no such program has been implemented. The cause of the geographical differences in the prevalence of gastric cancer most probably is increased prevalence of Helicobacter pylori (Hp) in East Asia as well as a higher frequency of atrophic oxyntic gastritis (4). The prognosis of gastric cancer is better in patients from East Asia even when living in the west possibly due to less aggressive biology (5). In this review, we will focus on the role of gastrin in the etiology of gastric cancer and at the same time give an explanation of the decline in frequency. We will only cover cancers originating from epithelial cells (carcinomas) and will not discuss the importance of Epstein-Barr virus that plays a role neither in gastric carcinogenesis (6) nor in human papilloma virus, which has a less established impact (7).