Cancer High-Risk Subjects Identified by Serum Pepsinogen Tests: Outcomes after 10-Year Follow-up in Asymptomatic Middle-Aged Males

Abstract

Background: Gastric cancer screening using the pepsinogen filter test is receiving wide recognition in Japan owing to convenience, freedom from discomfort or risk, efficiency, and economy. Because the long-term outcomes of cancer development in extensive atrophic gastritis detected by pepsinogen test are unclear, testpositive and test-negative subjects were investigated in a longitudinal cohort study. Methods: Subjects comprised 5,209 middle-aged men with measured serum pepsinogen levels who were followed for 10 years. Cancer development based on ''atrophy-positive'' and ''atrophy-negative'' criteria used for cancer screening was investigated. Results: During the study, 63 cases of cancer developed in the cohort, representing an incidence rate of 125 per 100,000 person-years. Pepsinogen test screening using the most widely used atrophy-positive criterion (pepsinogen I, V70 ng/mL; pepsinogen I/II ratio, V3.0) displayed 58.7% sensitivity, 73.4% specificity, and 2.6% positive predictive value. Cancer inci-

Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis

“…Serum PG levels are generally used for the detection of H. pylori-infection related atrophic gastritis on the basis of the previously described PG test positive criteria (PG I B70 ng/ml and PG I/II ratio B3.0) [10]. Then we compared with methylation levels between subjects with and without gastric atrophy according to the criteria.…”

“…In contrast, correlations between activity of gastritis and altered mucosal DNA methylation levels have not been reported. Activity of gastritis is reportedly correlated with the development of diffuse-type gastric cancer [10,13]. We therefore hypothesized that the degree of altered DNA methylation in stomach mucosae is correlated with activity of gastritis, since methylation observed in inflammatory stomach mucosae would directly or indirectly induce diffuse-type cancer development.…”

“…In terms of correlations between activity of H. pylori-related gastritis and incidence of gastric cancer, two serum markers have been evaluated: H. pylori antibody and pepsinogen (PG) II [9,10]. Both the titer of serum H. pylori antibody, which is usually used for determining the current status of the bacterial infection, and PG II, an aspartic protease also known as an inactive precursor of pepsin C produced mainly by the stomach mucosae, have been shown to correlate with the activity of H. pylori-related gastritis [11,12].…”

“…Both the titer of serum H. pylori antibody, which is usually used for determining the current status of the bacterial infection, and PG II, an aspartic protease also known as an inactive precursor of pepsin C produced mainly by the stomach mucosae, have been shown to correlate with the activity of H. pylori-related gastritis [11,12]. In addition, our previous reports have indicated that individuals with H. pylori antibody titers [500 U/ml or PG II levels [30 ng/ml are at high risk of developing gastric cancer, particularly diffuse-type cancer according to Lauren's histopathological classification [10,13]. Ito et al [14] also reported that patients with PG II [30 ng/ml show an increased risk of diffuse-type gastric cancer.…”

Aberrant Methylation of RASGRF1 Is Associated with an Epigenetic Field Defect and Increased Risk of Gastric Cancer

“…its evaluation based on serum pepsinogen tests is a useful means of assessing cancer risk (12,20). To evaluate the relationship between RASGRF1 methylation and mucosal atrophy, we divided the samples based on the pepsinogen test results and then generated respective ROC curves.…”