Sasazuki S et al. (2006) Effect of Helicobacter pylori infection combined with CagA and pepsinogen status on gastric cancer development among Japanese men and women: a nested case-control study. Cancer Epidemiol Biomarkers Prev 15: 1341–1347

Helicobacter pylori infection is thought to have a role in gastric carcinogenesis, but risk estimates vary widely. Researchers from the Japan Public Health Center Study Group conducted a large nested case–control study within a prospective cohort to evaluate the magnitude of the association and the effect of CagA and pepsinogen status on this relationship.

From a total of 123,576 subjects, 511 cases of gastric cancer were included in the study, and matched to 511 controls. The risk of gastric cancer was raised fivefold in patients with H. pylori seropositivity as determined by IgG antibody testing. Among these patients, CagA seropositivity, which is associated with more-extensive inflammation and an increased likelihood of progression to atrophic gastritis, further increased the risk. Furthermore, CagA positivity was associated with a threefold increased risk of gastric cancer in H. pylori IgG-negative patients, indicating that a single test for H. pylori IgG might not identify all H. pylori cases. The risk of gastric cancer was much greater in those with pepsinogen levels indicative of atrophic gastritis than in those with normal mucosa; risk increased with increasing severity of atrophic gastritis.

The authors comment that controlling H. pylori infection could decrease the risk of gastric cancer, but screening for H. pylori is expensive and can lead to misclassification. Patients with pepsinogen levels indicating severe atrophic gastritis may need to receive regular examination irrespective of H. pylori status; H. pylori-seropositive patients with lower pepsinogen levels would probably benefit from H. pylori eradication therapy.