Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer

Abstract

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4,655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100,000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. Despite a worldwide decline in incidence, gastric cancer remains one of the leading causes of cancer-related death in Japan. [1][2][3][4] There is a marked geographic variability in the gastric cancer incidence rate; the cancer is most common in China and Japan, and one of the lowest rates is in the United States. [1][2][3][4] Many epidemiologic studies have shown that the risk of gastric cancer is strongly associated with environmental factors, such as salt, nitrates and low intake of fresh fruits and vegetables. 1,4 -8 Recent studies have indicated that Helicobacter pylori infection is also a major risk factor for the development of gastric cancer. 9 -18 The prevalence of H. pylori infection is markedly higher in Japan than in other industrialized countries, although the reasons are not fully understood. 19 -21 The observed geographic variability in gastric cancer appears to be explained by a synergistic interaction between H. pylori infection and other environmental factors.The H. pylori bacterium colonizes the stomach mucosa and triggers a series of inflammatory reactions. It is considered an important cause of chronic atrophic gastritis (CAG), 19 -23 as shown in rodent models. 24 -26 CAG is considered the first step of a sequence of mucosal changes in the stomach leading to cancer. The current model for stomach carcinogenesis begins with gastritis, proceeds to CAG, then to intestinal metaplasia, dysplasia and, finally, carcinoma. 1,27 This hypothesis is supported by a considerable number of clinicopathological and epidemiological studies in countries with a high incidence of gastric cancer. However, longitudinal cohort studies that report an association of CAG with gastric cancer and a relation between the progression of CAG and the development of gastric cancer are limited. 28 -30 In addition, the role of H. pylori infection in the above-mentioned process of stomach carcinogenesis remains unclear. To investigate these problems relating to gastric cancer development, we established a cohort of male factory workers that we followed prospectively for 8 years.CAG in a high-risk population, such as Japanese subjects, usually begins at the gastric antrum and extends proximally towards the cardia. [31][32][33] As a result, gastric secretory function diminishes as the area of functional fundic gland mucosa gets smaller. 34 CAG is a histopathological diagnosis. It is difficult, howe...

A nested case–control study of the association of Helicobacter pylori infection with gastric adenocarcinoma in Korea

“…The study participants were mostly farmers, so a generalisation with respect to the entire Korean population cannot be assumed. The disappearance of incidence of childhood infection may have introduced temporality bias (Ohata et al, 2004). The history of gastric ulcer or gastritis did not affect the association of H. pylori infection to gastric cancer in our data (data not shown).…”

Preventive effects of etodolac, a selective cyclooxygenase‐2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori‐negative precancerous lesion

“…Several previous studies have demonstrated that the more advanced the stage of H. pylori-related CAG, the greater the cancer risk. 31,32,[40][41][42][43][44] Subjects with metaplastic gastritis, an end result of long-lasting H. pylori infection, are thus considered to be at particularly high risk of gastric cancer. Indeed, our previous longitudinal cohort study found that a group of middle-aged male subjects with metaplastic gastritis based on 2 serum tests-negative results for H. pylori antibody and positive results on the PG test-displayed an annual cancer incidence rate of about 0.87%, meaning that 1 cancer developed in 11.5 subjects during every 10-year period.…”

“…Indeed, our previous longitudinal cohort study found that a group of middle-aged male subjects with metaplastic gastritis based on 2 serum tests-negative results for H. pylori antibody and positive results on the PG test-displayed an annual cancer incidence rate of about 0.87%, meaning that 1 cancer developed in 11.5 subjects during every 10-year period. 31,32 Subjects selected for the present study were early cancer patients curatively treated with endoscopic resection and thus appear to constitute a subgroup at even higher risk for gastric cancer among subjects with metaplastic gastritis. A few previous studies have reported an annual incidence of metachronous cancer after endoscopic resection of about 1.3-4.0%, 45,46 while the annual cancer incidence rate in the present study was Figure 1.…”

Incidence of chronic atrophic gastritis: systematic review and meta-analysis of follow-up studies

“…Chronic atrophic gastritis (CAG) is an important precursor lesion in the development of intestinal type of gastric cancer [1]. Even though there is a worldwide decline in the incidence of this type of cancer, its public health burden is still high, with gastric cancer ranking fourth in cancer incidence and being the second most common cause of cancer-related deaths worldwide [2].…”