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

Author:

Sasazuki Shizuka1,Inoue Manami1,Iwasaki Motoki1,Otani Tetsuya1,Yamamoto Seiichiro2,Ikeda Shinobu1,Hanaoka Tomoyuki1,Tsugane Shoichiro1,

Affiliation:

1. 1Epidemiology and Prevention Division and

2. 2Statistics and Cancer Control Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan

Abstract

Abstract Background: Although accumulating evidence suggests that Helicobacter pylori plays a role in gastric carcinogenesis, the magnitude of the risk remains uncertain. Aim: We aimed to estimate the magnitude of the risk of gastric cancer associated with H. pylori infection by a large case-control study nested within a prospective cohort. Possible effect modification by CagA status, and serum pepsinogen status, as a marker of atrophic gastritis, was also considered to see its effect on developing gastric cancer. Subjects and Methods: Subjects (n = 123,576) were followed up from 1990 to 2004; 511 gastric cancer cases matched to 511 controls were used in the analysis. Plasma immunoglobulin G antibody to H. pylori, CagA, and pepsinogen I and II were measured. Results: The adjusted odds ratio (95% confidence interval) of gastric cancer associated with H. pylori infection was 5.1 (3.2-8.0). Assuming all CagA-positive subjects are true H. pylori positives doubled this risk. Atrophic gastritis was also associated with an elevated risk of gastric cancer and the risk increased further with pepsinogen levels. Conclusions: Subjects with pepsinogen levels indicative of severe atrophic gastritis may need careful examination regularly regardless of H. pylori infection. Those who have other pepsinogen levels but who are H. pylori seropositive are likely to benefit from H. pylori eradication therapy. Considering both the cost and the potential for misclassification that may occur using multiple serologic tests, caution is needed in interpreting or extrapolating these findings into a screening strategy. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1341–7)

Publisher

American Association for Cancer Research (AACR)

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