Braf, Kras and Helicobacter pylori epigenetic changes-associated chronic gastritis in Egyptian patients with and without gastric cancer.
We aimed to study MLH1 and MGMT methylation status in Helicobacter pylori-associated chronic gastritis in Egyptian patients with and without gastric cancer. 39 patients were included in our study. They were divided into 2 groups; patients without (group I) and with gastric adenocarcinoma (group II). Patients were subjected to clinical examination, abdominal ultrasound and upper endoscopy for gastric biopsy. Biopsies were subjected to urease test, histological examination, and DNA purification. H. pylori, Braf, Kras, MLH1 and MGMT methylation were assessed by quantitative PCR. DNA sequencing was performed to assess Braf and Kras genes mutation. qPCR of H. pylori was significantly higher in patients with adenocarcinoma (group II) than those without adenocarcinoma (group I); with a p < 0.001 as well as in patients with age above 50 years with a p value = 0.008. By applying logistic regression analysis it was reported that the H. pylori qPCR is a significant predictor to the adenocarcinoma with OR = 1.025 (95 % CI: 1. 002-1.048), with sensitivity of 90 % and specificity of 100 %. Adenocarcinoma patients had a significantly higher mean age and levels of H. Pylori, Braf, K-ras, methylated MGMT and methylated MLH1 than those of gastritis patients. DNA sequence analysis of Braf (codon 12) and Kras (codon 600) had genes mutation in gastric adenocarcinoma versus chronic gastritis.


CONCLUSIONS
H. pylori may cause epigenetic changes predisposing the patients to cancer stomach. Estimation of H. pylori by qPCR can be a good predictor to adenocarcinoma. Braf and Kras genes mutation were reveled in gastritis and adenocarcinoma patients.
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Giza, Egypt. dinasabry@kasralainy.edu.eg.
Dina
D
Sabry
Endemic Medicine & Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt.
Rasha
R
Ahmed
Internal Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt.
Sayed
S
Abdalla
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Giza, Egypt.
Wael
W
Fathy
Medical Biochemistry Department, Faculty of Medicine, October 6 University, Giza, Egypt.
Ahmed
A
Eldemery
Medical Biochemistry Department, Faculty of Medicine, El Fayoum University, Al Fayoum, Egypt.
Azza
A
Elamir
D000230:Adenocarcinoma / Q000235:genetics / Q000382:microbiology; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004534:Egypt; D044127:Epigenesis, Genetic; D005260:Female; D005756:Gastritis / Q000201:enzymology / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D020869:Gene Expression Profiling; D016481:Helicobacter Infections / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics
C117307:KRAS protein, human; C501486:MLH1 protein, human; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras); D045643:DNA Repair Enzymes
Braf; Epigenetics; H.pylori; Kras