The influence of Helicobacter pylori eradication on the expression and methylation status of the FHIT gene in non-cancerous gastric mucosa of dyspeptic patients.

OBJECTIVE: To investigate the effect of Helicobacter pylori (H. pylori) eradication on the expression level of the FHIT gene and its methylation status in the gastric mucosa of dyspeptic patients with or without a family history of gastric cancer (FHGC). METHODS: In all, 31 patients with H. pylori infection including 13 with FHGC were enrolled in the study. The effectiveness of H. pylori eradication were confirmed by UBT, RUT and multiplex PCR (the presence of selected H. pylori strains) for biopsy samples from the antrum and corpus. Histopathological assessment was also performed. The expression of FHIT mRNA was determined by quantitative reverse transcription-polymerase chain reaction and the methylation status of the FHIT promoter was assessed by methylation-specific polymerase chain reaction. RESULTS: After H. pylori eradication, the improvement of inflammation from superficial gastritis to normal mucosa (G → N) was observed in 39% of the patients without FHGC and in 54% of those with FHGC. FHIT mRNA expression was increased in patients without FHGC after H. pylori eradication (P < 0.05), while there was no statistically significant change in gene methylation status after H. pylori eradication (P > 0.05). For the samples from those with FHGC, the FHIT mRNA expression was not significantly changed and the methylation status fluctuated evenly. CONCLUSIONS: H. pylori eradication results in the improvement of gastric mucosal inflammation and histopathological non-atrophic changes. The FHIT gene expression is increased in patients without FHGC, which may contribute to the prevention of GC development.

Family history of gastric cancer correlates with decreased expression of HINT1 tumor suppressor gene in gastric mucosa of dyspeptic patients.

Gastric cancer (GC) is the fourth most common cancer and the second most common cause of cancer-associated mortality worldwide. Approximately 10% of gastric cancers are hereditary and a small percentage of these cases (1-3%) have been classified as a single hereditary syndrome (hereditary diffuse gastric cancer). We previously demonstrated that a family history of gastric cancer (FHGC) contributes to a predisposition towards the development of gastric cancer. Our data revealed that for dyspeptic patients whose first-degree relative(s) succumbed to GC, the levels of the fragile histidine triad pro-apoptotic protein in gastric mucosa were decreased. Another member of the histidine triad protein superfamily is histidine triad nucleotide-binding protein 1 (HINT1), a novel tumor suppressor that plays an inhibitory role in the control of gene transcription. The study comprised 38 ethnically homogeneous patients with dyspeptic symptoms without concomitant chronic diseases (18 controls/20 patients with FHGC). The results showed that the samples from the control patients predominantly exhibited non-atrophic changes (approximately 90%), whereas atrophic changes occurred more frequently in patients with FHGC. Notably, the expression levels of the HINT1 gene were markedly higher in the samples with atrophy taken from the antrum of FHGC patients compared to the non-atrophic samples. Moreover, the levels of HINT1 mRNA in samples obtained from the antrum of patients with FHGC were lower compared to analogous samples from the control individuals. The decreased levels of HINT1 mRNA in the antrum samples of patients with the FHGC indicate that it is a factor predisposing those patients to the development of gastric cancer.