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Clinical Cancer Research Vol. 9, 5245-5251, November 1, 2003
© 2003 American Association for Cancer Research


Molecular Oncology, Markers, Clinical Correlates

Higher Gastric Cycloxygenase-2 Expression and Precancerous Change in Helicobacter pylori-Infected Relatives of Gastric Cancer Patients

Bor-Shyang Sheu1, Hsiao-Bai Yang, Shew-Meei Sheu, Ay-Huey Huang and Jiunn-Jong Wu

Departments of Internal Medicine [B-S. S.], Pathology [H-B. Y., A-H. H.], and Medical Technology [J-J. W.], and Institute of Basic Science [S-M. S.], Medical College, National Cheng Kung University, Tainan 70428, Taiwan

Purpose: This study was conducted to determine whether relatives of gastric cancer patients (GCF) showed greater gastric cycloxygenase-2 (COX-2) expression or a greater incidence of precancerous lesions after Helicobacter pylori infection and whether H. pylori eradication could reduce COX-2 expression.

Experimental Design: Three hundred subjects were enrolled in this study: half were relatives of 50 H. pylori-infected gastric cancer patients, and half were relatives of 50 H. pylori-infected duodenal ulcer (DU) patients (controls). Each relative underwent endoscopy to detect H. pylori infection and related gastric histology. One hundred and twenty GCFs were found to have H. pylori infection. After H. pylori eradication, 90 of the 120 GCFs were followed up with annual endoscopy examinations over the next 2 years. Gastric COX-2 intensity in all of the specimens collected from these patients was immunochemically stained and graded from 0 to 4.

Results: H. pylori infection, gastric atrophy, and intestinal metaplasia (IM) were more prevalent in GCFs than in relatives of H. pylori-infected patients with DUs (P < 0.05). H. pylori-infected GCFs also showed a greater COX-2 intensity than H. pylori-infected relatives of patients with DUs (89.1% versus 62.7%, P < 0.001; relative risk: 4.9; 95% confidence interval: approximately 2.34–10.29). Among the H. pylori-infected GCFs, COX-2 intensity correlated with atrophy and IM (P < 0.001). After H. pylori eradication, gastric COX-2 expression disappeared only in those relatives without IM (P < 0.001).

Conclusions: GCFs are more likely to show greater gastric COX-2 expression and a higher incidence of precancerous lesions after H. pylori infection than the relatives of H. pylori-infected patients with only DUs. H. pylori eradication can reverse gastric COX-2 expression in patients without IM but not in patients with IM.




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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Copyright © 2003 by the American Association for Cancer Research.