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

<jats:title>Abstract</jats:title><jats:p>A total of 5,209 asymptomatic, middle‐aged subjects, whose serum pepsinogen (PG) and <jats:italic>Helicobacter pylori</jats:italic> antibody levels had been assessed, were followed for 10 years. Subjects with positive serum <jats:italic>H. pylori</jats:italic> antibodies (>50 U/mL) had an increased cancer risk (HR = 3.48, 95% CI = 1.26–9.64). Risk of gastric cancer increased as the antibody level increased; the <jats:italic>H. pylori</jats:italic>‐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 = 3.54, 95% CI = 1.95–6.40) or PG I/II ratio ≤3.0 (HR = 4.25, 95% CI = 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 = 3.81, 95% CI = 1.10–13.21). Using <jats:italic>H. pylori</jats:italic> antibody and PG levels, subgroups with an especially high or low cancer incidence rate could be identified. <jats:italic>H. pylori</jats:italic>‐negative or indeterminate subjects with low PG level (PG I ≤30 ng/mL or PG I/II ratio ≤2.0) or <jats:italic>H. pylori</jats:italic>‐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, <jats:italic>H. pylori‐</jats:italic>negative 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 <jats:italic>H. pylori</jats:italic> antibody levels can be used to predict the risk of cancer in individuals with <jats:italic>H. pylori‐</jats:italic>related gastritis from the general population. © 2008 Wiley‐Liss, Inc.</jats:p>