[Genetics and environmental factors in gastric carcinogenesis].

BACKGROUND: Gastric cancer is considered to be the second most common cancer worldwide. Carcinogenesis of the stomach is a multi-stage process. The progression from normal epithelial to tumor cells may involve at least five stages: superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia and carcinoma. These sequential changes in the gastric mucosa may occur over a period of many years as a result of exposure to a variety of exogenous and/or endogenous factors which cause genetic alterations. Recent developments in molecular genetics have shown that the accumulation of these multiple genetic alterations, including activation of oncogenes and inactivation of tumor-suppressor genes, results in cancer development. Genetic alterations previously reported in gastric carcinomas include amplifications or mutations of the c-ERBB2, K-RAS, c-MET and TP53. Chromosomal gains were also found in various combinations with chromosomal losses and may be associated with the overexpression of dominant oncogenes contributing to tumor progression.

CONCLUSIONS: These accumulated genetic changes in carcinomas provide evidences for the stepwise mode of gastric carcinogenesis through the accumulation of a series of genetic alterations.