Author/Authors :
Sabry, Dina Cairo University - Faculty of Medicine - Medical Biochemistry, Egypt , Ahmed, Rasha Cairo University - Faculty of Medicine - Endemic Medicine, Egypt , Fouad, Ahmed Cairo University - Faculty of Medicine - Endemic Medicine, Egypt , Abdalla, Sayed Cairo University - Faculty of Medicine - Internal Medicine, Egypt , Abul Fotouh, Amr Cairo University - Faculty of Medicine - Endemic Medicine, Egypt , Kamal, Manal Cairo University - Faculty of Medicine - Chemical pathology, Egypt , Omar, Dina Cairo University - Faculty of Medicine - Pathology, Egypt , Fawzy, Mai Cairo University - Faculty of Medicine - Internal Medicine, Egypt , Darwish, Tarneem Cairo University - Faculty of Medicine - Biomedical informatician, Egypt
Abstract :
Previous reports have indicated that Helicobacter pylori (H. pylori) causes epigenetic changes that may be associated with carcinogenesis. In our study we focused on MLHl and MGMT methylation in H. pyloriassociated chronic gastritis in Egyptian patients with and without gastric cancer and sequencing of BRAF and KRAS in some samples. Twenty nine patients with H.pylori associated gastritis (group I) and ten patients with histologically proven gastric adenocarcinoma (group II) were recruited in this study from patients attending to endoscopy unit, Cairo university in the period from August to December 2011. Patients were subjected to thorough history and clinical examination, abdominal ultrasound and upper endoscopy where patients with gastric lesion suggestive of gastritis and/or malignancy were endoscopically biopsied and examined by urease test. Biopsies were subjected to histological examination, and DNA purification. The mean level of H.pylori PCR was significantly higher in patients with adenocarcinoma with a p 0.001 as well as in patients with age above 50 years with ap value -0.008. By applying logistic regression analysis we found that the H pylori qPCR is a significant predictor to the adenocarcinoma with OR= J.025 (95% CI: 1.002-1.048), with sensitivity of 90%, specificity of 100%. Adenocarcinoma patients had a significantly higher mean age and have significantly higher levels of H.Pylori, BRAF, KRAS, methylated MGMT and Methylated MLHl than those of gastritis patients. DNA sequence analysis was done in a subset of patients from both groups and revealed that BRAF (codon 12 ) had C transition to Tin gastric adenocarcinoma. DNA sequence while KRAS (codon 600) had T transition to A in gastric adenocarcinoma. Conclusion: H. pylori can cause epigenetic changes predisposing the patients to cancer stomach. Assessment of the level of H. pylori by qPCR can be a good predictor to adenocarcinoma. Gene sequencing for the BRAF and KRAS genes, in samples from the gastritis and adenocarcinoma patients revealed mutation of both genes in adenocarcinoma.
