The Clinical Evidence Linking Helicobacter pylori to Gastric Cancer

Abstract

Gastric cancer has long been recognized to be accompanied and preceded by chronic gastritis, lasting decades. Arguably, the most important development in our understanding of gastric cancer pathogenesis over the past 50 years has been the realization that, for most cases of gastric cancer, Helicobacter pylori is the cause of the underlying gastritis. Gastritis can promote gastric carcinogenesis, typically via the Correa cascade of atrophic gastritis, intestinal metaplasia, and dysplasia. Nested case-control studies have shown that H pylori infection increases the risk of gastric cancer significantly, both of the intestinal and diffuse subtypes, and that H pylori is responsible for approximately 90% of the world's burden of noncardia gastric cancer. Based largely on randomized studies in high gastric cancer prevalence regions in East Asia, it appears that primary and tertiary intervention to eradicate H pylori can halve the risk of gastric cancer. Some public health authorities now are starting screening and treatment programs to reduce the burden of gastric cancer in these high-risk areas. However, there is currently much less enthusiasm for initiating similar attempts in the United States. This is partially because gastric cancer is a relatively less frequent cause of cancer in the United States, and in addition there are concerns about theoretical downsides of H pylori eradication, principally because of the consistent inverse relationship noted between H pylori and esophageal adenocarcinoma. Nevertheless, establishing a link between chronic H pylori infection and gastric cancer has led to novel insights into cancer biology, the gastrointestinal microbiome, and on individual and population-based gastric cancer prevention strategies.

Keywords: CI, confidence interval; Cancer Prevention; ELISA, enzyme-linked immunosorbent assay; Epidemiology; Gastric Cancer; Helicobacter pylori.

Figure 1

Three pathologists who shaped our understanding of H pylori–induced gastric carcinogenesis.Left to right: Rudolf Virchow, Pelayo Correa, and Robin Warren. Reproduced with permission from: https://commons.wikimedia.org/wiki/File:Rudolf_Virchow_NLM3.jpg; and http://news.vicc.org/2013/06/correa-honored-for-gastroenterological-research/.

Figure 2

Current model of the decades-long sequence of intestinal-type gastric carcinogenesis, based on the classical histopathologic Correa cascade in grey box (left), with (center) postulated stimuli (green boxes) and mechanisms (red boxes), and some of the key accompanying molecular genetic events (right).

Figure 3

Complex relationship between H pylori and the common cancers of the esophagus and stomach. Data are shown as odds ratios for the development of cancer in H pylori–infected vs uninfected persons.