Review
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World J Gastroenterol. Mar 21, 2006; 12(11): 1671-1680
Published online Mar 21, 2006. doi: 10.3748/wjg.v12.i11.1671
Helicobacter pylori eradication to prevent gastric cancer: Underlying molecular and cellular mechanisms
Shingo Tsuji, Masahiko Tsujii, Hiroaki Murata, Tsutomu Nishida, Masato Komori, Masakazu Yasumaru, Shuji Ishii, Yoshiaki Sasayama, Sunao Kawano, Norio Hayashi
Shingo Tsuji, Masahiko Tsujii, Hiroaki Murata, Tsutomu Nishida, Masakazu Yasumaru, Shuji Ishii, Norio Hayashi, Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine (K1), Yamadaoka, Suita, 565-0871 Japan
Masato Komori, Department of Internal Medicine, Kansai Rohsai Hospital, Amagasaki, 660-0064 Japan
Yoshiaki Sasayama, Department of Internal Medicine, Kashiwara Muncipal Hospital, Kashiwara, 582-0002 Japan
Sunao Kawano, Department of Clinical Laboratory Science, Osaka University Graduate School of Medicine, Suita, 565-0871 Japan
Correspondence to: Shingo Tsuji, MD, PhD, Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine (K1), 2-2 Yamadaoka, Suita, 565-0871 Japan. tsuji@medone.med.osaka-u.ac.jp
Telephone: +81-6-68793626 Fax: +81-6-68793629
Received: September 13, 2005
Revised: September 25, 2005
Accepted: November 10, 2005
Published online: March 21, 2006
Abstract

Numerous cellular and molecular events have been described in development of gastric cancer. In this article, we overviewed roles of Helicobacter pylori (H pylori) infection on some of the important events in gastric carcinogenesis and discussed whether these cellular and molecular events are reversible after cure of the infection. There are several bacterial components affecting gastric epithelial kinetics and promotion of gastric carcinogenesis. The bacterium also increases risks of genetic instability and mutations due to NO and other reactive oxygen species. Epigenetic silencing of tumor suppressor genes such as RUNX3 may alter the frequency of phenotype change of gastric glands to those with intestinal metaplasia. Host factors such as increased expression of growth factors, cytokines and COX-2 have been also reported in non-cancerous tissue in H pylori-positive subjects. It is noteworthy that most of the above phenomena are reversed after the cure of the infection. However, some of them including overexpression of COX-2 continue to exist and may increase risks for carcinogenesis in metaplastic or dysplastic mucosa even after successful H pylori eradication. Thus, H pylori eradication may not completely abolish the risk for gastric carcinogenesis. Efficiency of the cure of the infection in suppressing gastric cancer depends on the timing and the target population, and warrant further investigation.

Keywords: Helicobacter; Cancer; Gastric acid; p53; In-flammation; Gastric atrophy; Intestinal metaplasia