Helicobacter pylori eradication to prevent gastric cancer: underlying molecular and cellular mechanisms.
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.
Tsuji
Shingo
S
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
Tsujii
Masahiko
M
Murata
Hiroaki
H
Nishida
Tsutomu
T
Komori
Masato
M
Yasumaru
Masakazu
M
Ishii
Shuji
S
Sasayama
Yoshiaki
Y
Kawano
Sunao
S
Hayashi
Norio
N
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D044127:Epigenesis, Genetic; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000503:physiopathology* / Q000628:therapy; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D008679:Metaplasia / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology* / Q000473:pathology* / Q000517:prevention & control; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014774:Virulence
D050677:Core Binding Factor Alpha 3 Subunit; D016207:Cytokines; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; C493729:Runx3 protein, human; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human