Carcinogenesis and Infection with Helicobacter pylori GIANINA MICU 1 , FLORICA STĂNICEANU 1,2 , SABINA ZURAC 1,2 , ALEXANDRA BASTIAN 1 , ELIZA GRAMADĂ 1 , LUCIANA NICHITA 1,2 , CRISTIANA POPP 1 , LIANA STICLARU 1 , R. ANDREI 1 , C. SOCOLIUC 1 1 “Colentina” Clinical Hospital, Department of Pathology, Bucharest, Romania 2 “Carol Davila” University of Medicine, Bucharest, Romania It was accepted several years ago that, in the carcinogenesis process of human cancers, biologic agents, especially the viruses, are playing an etiologic role. This is the case of lymphomas (retroviruses), hepatocarcinoma (hepatic viruses) and cervical carcinoma (papilloma viruses). Helicobacter pylori is the first bacteria recognized as a first class carcinogen for gastric cancer. Nevertheless, comparing with the most validated human carcinogens, the activity of H. pylori is very little studied. As a consequence, at this moment, in its case, explanation of carcinogenesis mechanism is more or less hypothetical. Key words: Helicobacter pylori, CagA, VacA, carcinogenesis, epithelial premalignant lesions, lymphoid malignities. THE EPIDEMIOLOGICAL PERSPECTIVE In the last fifty years we witnessed a significant decrease of gastric cancer incidence in the developed countries population. An important contribution to this decrease was brought by the Japanese school of gastroenterology [1] [3] by healing of early gastric cancers in over 90% cases. Even so, at a world level, this terrible disease continues to be a front- runner among cancer-caused deaths (2 nd place) and it is considered the world’s 14 th cause of mortality [1]. Until H. pylori (Fig. 1) to become known as a direct carcinogen [2], the association of the H. pylori gastric infection with different gastric lesions was considered a facilitating (and not inductive) factor for carcinogenesis through the induction of intestinal metaplasia, glandular atrophy and hypochlorhydria followed by the accumulation of N-nitrous carcino- genic components, through the free radicals-gene- rating inflammatory reaction and excessive cellular proliferation. Afterwards it was demonstrated that bacteria not only favour, but also produce malign modify- cations at the level of the gastric mucosa: both histological variants of antral gastric adenocarcinoma (the intestinal type and the diffuse type, according to the Lauren classification) and the gastric lym- phoma, without being implicated in eso-cardial junction cancers. Cardial lesions appear in patients with a significant gastro-oesophageal reflux, and in this case H. pylori infection can have a protective role [4]. Recently, sero-epidemiological studies ap- proximate that at least 70% of diagnosed gastric carcinomas have Helicobacter pylori as a determining cause [3] [4], and the serologic presence of HP antibodies was demonstrated at least ten years before the disease was diagnosed. The arguments belong to descriptive epidemio- logy that presents a geographical distribution [3][5] of the gastric cancer overlapped by that of Helicobacter pylori infection. In countries with a high presence of gastric cancer, the incidence of Helicobacter pylori infection is also high. These observations are also sustained by the conclusions of the epidemiological studies that show a high frequency of the gastric cancer in patients that belong to economically disadvantaged classes, subjects that also proved to have a significantly high incidence of the infection [1] [6]. Epidemiological paradoxes From the researchers in epidemiology point of view there are still several unsolved paradoxes: – Why, even if H. Pylori infection affects about half of the planet’s population, only very few subjects develop a gastric cancer? [7] Explanations for this situation are probably in the role of genetic and diet factors. – On the other hand, even if H. pylori in- fection has a relatively even distribution in both sexes, why does the gastric cancer affect mainly men? [4] [7] ROM. J. INTERN. MED., 2010, 48, 4, 299–306