Helicobacter pylori infection and family history of gastric cancer decrease expression of FHIT tumor suppressor gene in gastric mucosa of dyspeptic patients.
BACKGROUND
The expression of a fragile histidine triad (FHIT) protein is lost in stomach tumors. The study aimed at determining whether FHIT expression is affected by Helicobacter pylori infection, strain virulence (vacA and cagA genes) and histopathological changes in the gastric mucosa of patients with functional dyspepsia having first-degree relatives with gastric cancer.


METHODS
Eighty-eight never-smoking patients with functional dyspepsia were selected for the study, and 48 of them had first-degree relatives with gastric cancer. Bacterial DNA amplification was used to identify H. pylori colonization. The level of FHIT gene expression was determined by qRT-PCR (mRNA) and Western blot (FHIT protein) analyses.


RESULTS
For patients having first-degree relatives with gastric cancer FHIT expression was lower (mRNA by ca. 40-45% and protein by 30%) compared with the control patients (p < .05). H. pylori infection decreased the FHIT mRNA level by 10-35% and the protein level by 10-20%. Bacterial strain vacA(+)cagA(+) lowered FHIT mRNA by ca. 30-35% in the antrum samples of both groups and in corpus samples of patients with first-degree relatives with gastric cancer (p < .05). The FHIT mRNA level was twice as high in control H. pylori-negative patients with intestinal metaplasia, compared with those with non-atrophic gastritis.


CONCLUSIONS
The decreased FHIT gene expression associated with hereditary factors and with H. pylori infection, especially with vacA(+)cagA(+)-positive strains, may be related to gastric carcinoma development.
Stec-Michalska
Krystyna
K
Department of Gastroenterology and Internal Diseases, Medical University of Lodz, Hallera 1, 90-647 Lodz, Poland. stemii@wp.pl
Peczek
Lukasz
L
Michalski
Blazej
B
Wisniewska-Jarosinska
Maria
M
Krakowiak
Agnieszka
A
Nawrot
Barbara
B
D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D004415:Dyspepsia / Q000235:genetics* / Q000382:microbiology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D015870:Gene Expression; D016481:Helicobacter Infections / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D014774:Virulence; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase