Waldum Helge L, Hauso Øyvind, Sørdal Øystein F, Fossmark Reidar
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Prinsesse Kristinas Gate 1, 7006, Trondheim, Norway,
Dig Dis Sci. 2015 Jun;60(6):1522-7. doi: 10.1007/s10620-014-3468-9. Epub 2014 Dec 6.
Gastric cancer occurs almost exclusively in patients with gastritis. Since Helicobacter pylori (Hp) was proved to cause gastritis, Hp was also expected to play a role in gastric carcinogenesis. Despite extensive studies, the mechanisms by which Hp cause gastric cancer are still poorly understood. However, there is evidence that the anatomical site of Hp infection is of major importance. Infection confined to the antral mucosa protects against gastric cancer but predisposes to duodenal ulcer, whereas Hp infection of the oxyntic mucosa increases the risk of gastric cancer. Hp infection does not predispose to cancers in the gastric cardia. In patients with atrophic gastritis of the oxyntic mucosa, the intragastric pH is elevated and the concentration of microorganisms in the stomach is increased. This does not lead to increased risk of gastric cancer at all anatomical sites. The site specificity of Hp infection in relation to cancer risk indicates that neither Hp nor the changes in gastric microflora due to gastric hypoacidity are carcinogenic per se. However, reduced gastric acidity also leads to hypergastrinemia, which stimulates the function and proliferation of enterochromaffin-like (ECL) cells located in the oxyntic mucosa. The ECL cell may be more important in human gastric carcinogenesis than previously realized, as every condition causing long-term hypergastrinemia in animals results in the development of neoplasia in the oxyntic mucosa. Patients with hypergastrinemia will far more often develop carcinomas in the gastric corpus. In conclusion, hypergastrinemia may explain the carcinogenic effect of Hp.
胃癌几乎仅发生于胃炎患者。自从幽门螺杆菌（Hp）被证实可引发胃炎以来，人们也期望它在胃癌发生过程中发挥作用。尽管进行了广泛研究，但Hp导致胃癌的机制仍知之甚少。然而，有证据表明Hp感染的解剖部位至关重要。局限于胃窦黏膜的感染可预防胃癌，但易引发十二指肠溃疡，而胃体黏膜的Hp感染会增加患胃癌的风险。Hp感染不会引发贲门癌。在胃体黏膜萎缩性胃炎患者中，胃内pH值升高，胃内微生物浓度增加。但这并不会导致所有解剖部位患胃癌的风险增加。Hp感染与癌症风险的部位特异性表明，Hp本身以及胃酸过少导致的胃微生物群变化都不是致癌因素。然而，胃酸减少也会导致高胃泌素血症，从而刺激位于胃体黏膜的肠嗜铬样（ECL）细胞的功能和增殖。ECL细胞在人类胃癌发生过程中可能比之前认为的更为重要，因为在动物身上，每一种导致长期高胃泌素血症的情况都会导致胃体黏膜发生肿瘤。高胃泌素血症患者在胃体发生癌症的几率要高得多。总之，高胃泌素血症可能解释了Hp的致癌作用。
