Helicobacter pylori, cyclooxygenase-2 and evolution of gastric lesions: results from an intervention trial in China.

Abstract

To investigate the role of cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) in the process of Helicobacter pylori-induced gastric carcinogenesis, a prospective study based on an intervention trial was conducted in Linqu County, China. A total of 1401 subjects with histopathologic diagnosis were investigated at baseline, among those, 919 completed subsequent interventions (anti-H.pylori and/or celecoxib treatment). Expressions of COX-2 and Ki-67 were assessed by immunohistochemistry, and PGE2 levels were measured by enzyme immunoassay before and after interventions, respectively. We found a grade-response relationship between COX-2 expression level and risk of advanced gastric lesions at baseline. Stratified analysis indicated an additive interaction between COX-2 expression and H.pylori infection on the elevated risk of advanced gastric lesions. The odds ratios (ORs) for both factors combined were 9.31 [95% confidence interval (CI): 4.13-20.95] for chronic atrophic gastritis, 16.26 (95% CI: 7.29-36.24) for intestinal metaplasia and 21.13 (95% CI: 7.87-56.75) for dysplasia, respectively. After interventions, COX-2 expression and Ki-67 labeling index (LI) were decreased in anti-H.pylori group (OR: 1.65, 95% CI: 1.36-1.99 for COX-2; OR: 1.78, 95% CI: 1.49-2.12 for Ki-67) or anti-H.pylori followed by celecoxib group (OR: 1.41, 95% CI: 1.17-1.70 for COX-2; OR: 1.63, 95% CI: 1.37-1.94 for Ki-67). PGE2 levels were decreased in all treatment groups. Furthermore, the regression of gastric lesions was associated with the decrease of COX-2 expression or Ki-67 LI after interventions. Our findings indicate that H.pylori-induced COX-2/PGE2 pathways play an important role on the progression of precancerous gastric lesions in a Chinese population.

• Authors: Yang Zhang, Kai-Feng Pan, Lian Zhang, Jun-Ling Ma, Tong Zhou, Ji-You Li, Lin Shen, Wei-Cheng You
• Journal: Carcinogenesis (Carcinogenesis) Vol. 36 Issue 12 Pg. 1572-9 (Dec 2015) ISSN: 1460-2180 [Electronic] England
• PMID: 26449252 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Anti-Bacterial Agents
• Cyclooxygenase 2 Inhibitors
• Amoxicillin
• Cyclooxygenase 2
• PTGS2 protein, human
• Clarithromycin
• Celecoxib
• Dinoprostone
• Omeprazole

Topics

• Adult
• Amoxicillin (therapeutic use)
• Anti-Bacterial Agents (therapeutic use)
• Celecoxib (therapeutic use)
• China
• Clarithromycin (therapeutic use)
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase 2 Inhibitors (therapeutic use)
• Dinoprostone (metabolism)
• Double-Blind Method
• Female
• Helicobacter Infections (drug therapy, enzymology, microbiology)
• Helicobacter pylori (immunology)
• Humans
• Male
• Middle Aged
• Omeprazole (therapeutic use)
• Precancerous Conditions (drug therapy, enzymology, microbiology)
• Stomach (enzymology, immunology, microbiology)
• Stomach Neoplasms (enzymology, microbiology, prevention & control)