Risk of gastric cancer in asymptomatic, middle‐aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels

Abstract

A total of 5,209 asymptomatic, middle-aged subjects, whose serum pepsinogen (PG) and Helicobacter pylori antibody levels had been assessed, were followed for 10 years. Subjects with positive serum H. pylori antibodies (>50 U/mL) had an increased cancer risk (HR 5 3.48, 95% CI 5 1.26-9.64). Risk of gastric cancer increased as the antibody level increased; the H. pylori-positive group with antibody levels >500 U/mL had the highest incidence rate (325/100,000 person-years). Cancer development also increased with a reduced serum PG I level or a reduced PG I/II ratio; the risk was significantly elevated with serum PG I level ≤30 ng/mL (HR 5 3.54, 95% CI 5 1.95-6.40) or PG I/II ratio ≤3.0 (HR 5 4.25, 95% CI 5 2.47-7.32). Furthermore, the risk of diffuse-type cancer increased as PG II level increased; it was significantly elevated with PG II level ≥30 ng/mL (HR 5 3.81, 95% CI 5 1.10-13.21). Using H. pylori antibody and PG levels, subgroups with an especially high or low cancer incidence rate could be identified. H. pylori-negative or indeterminate subjects with low PG level (PG I ≤30 ng/mL or PG I/II ratio ≤2.0) or H. pylori-positive subjects with antibody levels >500 U/mL and a low PG level were among the subgroups with a high cancer incidence rate (over 400/100,000 person-years). In contrast, H. pylorinegative subjects with a PG I level >70 ng/mL or a PG I/II ratio >3.0 had the lowest risk; none of these subjects developed cancer. Thus, serum PG levels and/or H. pylori antibody levels can be used to predict the risk of cancer in individuals with H. pylorirelated gastritis from the general population. ' 2008 Wiley-Liss, Inc.Key words: gastric cancer; pepsinogen; Helicobacter pylori; chronic atrophic gastritis; intestinal metaplasia Stomach carcinogenesis in high-risk populations, including the Japanese population, is believed to begin with chronic active inflammation of the stomach mucosa, proceeding to extensive atrophy together with intestinal metaplasia, then to dysplasia, and finally to cancer. 1 Currently, Helicobacter pylori (H. pylori) is considered a major factor in the establishment of the carcinogenic sequence in the stomach. 2-12 H. pylori-related gastritis usually starts in the antrum and expands proximally towards the body of the stomach. [13][14][15] During this process, both multifocal atrophy and intestinal metaplasia develop, eventually leading to chronic atrophic gastritis (CAG) with extensive intestinal metaplasia. Several studies dealing with endoscopic biopsies or chromoendoscopic testing found that the progression of CAG increases the risk for cancer. 12,[16][17][18][19][20] Thus, an accurate and reliable evaluation of the extent of CAG is considered to be important for identifying individuals at high risk of cancer. The diagnosis of CAG is based on histopathology of the stomach mucosa. However, gastric endoscopy with biopsy is an invasive test and inappropriate for mass population screening. In addition, since CAG together with intestinal metaplasia is a multifocal process, it is difficult to ac...

976 H. pylori Seropositivity Before Age 40 and Subsequent Risk of Stomach Cancer: A Glimpse of the True Relationship?

“…In particular, the group with Hp-CSA-/CagA+, compared with the reference group seronegative with both tests, has an odds ratio as high as 68.0. This is consistent with a recent Japanese cohort study among middle-aged subjects [23]. There, a more than 100-fold excess risk of stomach cancer was noted in the group seronegative with H. pylori antibodies but with a low pepsinogen I:II ratio.…”

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

“…Subjects were divided into three groups according to PG II level: group II-0, PG II B10 ng/ml; group II-10, PG II [10 ng/ml and B30 ng/ml; group II-30, PG II [30 ng/ml. These thresholds were determined in a previous study according to the risk of gastric cancer [13].…”

“…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.…”

“…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.…”

Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis

“…We have reported that, besides progression of gastric mucosal atrophy, patients with severe gastric mucosal inflammation (high PG-II levels and/or high H. pylori antibody titers) are at high risk for gastric cancer, particularly diffuse-type carcinoma (Yanaoka et al, 2008b), and that in these patients H. pylori eradication may likely prevent gastric cancer (Yanaoka et al, 2009). In this study, the high-intake group had significantly lower H. pylori antibody titers and lower serum PG-II, suggesting that JA intake may be effective in preventing gastric cancer whose mechanism involves H. pylori-related active mucosal inflammation.…”