Helicobacter pylori eradication to prevent gastric cancer: Underlying molecular and cellular mechanisms

Table 1 Molecular alteration in the process of gastric carcinogenesis

Molecules	Major alterations	Comments	Category
p53	Mutation, LOH	Reported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions.	Tumor suppressor
APC	Mutation, LOH	Reported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions.	Tumor suppressor
DCC	LOH	Reported in intestinal-type adenocarcinomas. Related to cell adhesion	Tumor suppressor
CDH1	Mutation	Reported in diffuse-type adenocarcinomas.	Tumor suppressor
β-catenin	Mutation	Reported in intestinal-type adenocarcinomas.	Tumor suppressor
Fhit	LOH or deletion at chr. 3p14.2	Reported in diffuse-type and, in less frequency, intestinal-type adenocarcinomas, as well as some precancerous lesions.	Tumor suppressor
RUNX3	Hypermethylation	Related to TGF-β/SMAD signaling.	Tumor suppressor
K-ras	Mutation	Reported in intestinal-type adenocarcinomas. An element in signal transduction regulating cell proliferation, etc..	Oncogene
bcl-2	LOH	Reported in intestinal-type adenocarcinomas. Anti-apoptotic factor.	Oncogene
c-met	Amplification	Reported in diffuse-type and intestinal-type adenocarcinomas. The HGF receptor / tyrosine-kinase. Upregulation without mutation is also reported after mucosal injury.	Oncogene / Growth stimulus
c-erbB2	Amplification	Reported in intestinal-type adenocarcinomas. One of receptor-tyrosine kinases for EGF-family proteins.	Oncogene / Growth stimulus
Cyclin E	Amplification	Reported in diffuse-type and intestinal type adenocarciomas.	Cell cycle regulator
K-sam	Amplification	Reported in diffuse-type adenocarcinomas. One of bFGF receptor family proteins, FGFR2.	Oncogene
Mismatch repair (MMR) genes	Silencing due to hypermethylation	Reported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions. A possible source of mutations of other genes involving gastric carcinogenesis.	Determinants of microsatelite instability (MSI)
MMR genes	Mutation	Reported in diffuse-type and intestinal-type adenocarcinomas. There are conflicting data suggesting that mucosa with intestinal metaplasia is prone to and resistant to MSI.	Determinants of MSI
EGFR	Overexpression	Reported in diffuse-type and intestinal-type adenocarcinomas.	Growth stimulus
EGF	Overexpression	Reported in diffuse-type and intestinal-type adenocarcinomas.	Growth stimulus
TGF-α	Overexpression	Reported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions. Another EGF-family protein.	Growth stimulus
VEGF	Overexpression	Reported in diffuse-type and intestinal-type adenocarcinomas.	Angiogenic factor
iNOS	Overexpression	Reported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions and mucosa with H. pylori.	Enzyme
COX-2	Overexpression	Reported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions and mucosa with H. pylori. Cytokines and growth factors are possible inducer of COX-2.	Enzyme
ODC	Overexpression	Reported earlier in gastritis.	Enzyme
Telomerase	Activated	Enlongs telomere and prevents cell senescence.	Enzyme
CDXs	Overexpression	Reported in diffuse-type and intestinal-type adenocarcinomas, as well as precancerous lesions. Is involved in intestinal metaplasia.	Transcription factor
Ets1	Overexpression	A transcription factor involving angiogenesis.	Transcription factor
NF-κB	Overexpression	A transcription factor regulating expression of proinflammatory cytokines, chemokines, iNOS and COX-2.	Transcription factor
Sp-1	Overexpression	Reported in diffuse-type and intestinal-type adenocarcinomas.	Transcription factor
SC-1	Overexpression	Reported in diffuse-type adenocarcinomas.	Apoptosis receptor
Fas/CD95	Overexpression	Reported in diffuse-type adenocarcinomas.	Apoptosis receptor
E-cadherin	Mutation	Reported in diffuse-type and intestinal-type adenocarcinomas.	Cell adhesion
CD44	Splicing variant	Reported in diffuse-type and intestinal-type adenocarcinomas.	Cell adhesion
Gastrin	Elevation in serum	Elevation of amidated gastrin is reported. Transactivates EGF-family proteins.	Gut hormone