title: Oxidative DNA damage as a potential early biomarker of Helicobacter pylori associated carcinogenesis.
abstract: Helicobacter pylori infection is an established risk factor for gastritis, gastric ulcer, peptic ulcer and gastric cancer. CagA +ve H. pylori has been associated with oxidative DNA damage of gastric mucosa but their combined role in the development of gastric cancer is still unknown. Here we compare the combined expression of cagA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in normal, gastritis and gastric cancer tissues. Two hundred gastric biopsies from patients with dyspeptic symptoms, 70 gastric cancer tissue samples and 30 gastric biopsies from non-dyspeptic individuals (controls) were included in this study and 8-OHdG was detected by immunohistochemistry (IHC). Histological features and the presence of H. pylori infection were demonstrated by Hematoxylin and Eosin (HE), Giemsa and alcian blue-periodic acid-Schiff ± diastase (AB-PAS ± D) staining. DNA was extracted from tissues and polymerase chain reaction (PCR) performed to determine the presence of ureaseA and cagA genes of H. pylori. The results showed the presence of H. pylori in 106 (53 %) gastric biopsies out of 200 dyspeptic patients, including 70 (66 %) cases of cagA + ve H. pylori. The presence of cagA gene and high expression of 8-OHdG was highly correlated with severe gastric inflammation and gastric cancer particularly, in cases with infiltration of chronic inflammatory cells (36.8 % cagA + ve, 18 %), neutrophilic activity (47.2 %, 25.5 %), intestinal metaplasia (77.7 %, 35.7 %) and intestinal type gastric cancer (95 %, 95.4 %) (p ≤ 0.01). In conclusion, H. Pylori cagA gene expression and the detection of 8-OHdG adducts in gastric epithelium can serve as potential early biomarkers of H. Pylori-associated gastric carcinogenesis.
authors.affiliation: Immunology and Infectious Diseases Research Laboratory, Department of Microbiology, University of Karachi, Karachi, Pakistan, yaaasirz@hotmail.com.
authors.forename: Yasir
authors.initials: Y
authors.lastname: Raza
authors.forename: Adnan
authors.initials: A
authors.lastname: Khan
authors.forename: Amber
authors.initials: A
authors.lastname: Farooqui
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mubarak
authors.forename: Alex
authors.initials: A
authors.lastname: Facista
authors.forename: Syed Shakeel
authors.initials: SS
authors.lastname: Akhtar
authors.forename: Saeed
authors.initials: S
authors.lastname: Khan
authors.forename: Javed Iqbal
authors.initials: JI
authors.lastname: Kazi
authors.forename: Carol
authors.initials: C
authors.lastname: Bernstein
authors.forename: Shahana Urooj
authors.initials: SU
authors.lastname: Kazmi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D004249:DNA Damage / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005756:Gastritis / Q000235:genetics / Q000473:pathology* / Q000821:virology; D016481:Helicobacter Infections / Q000235:genetics / Q000473:pathology* / Q000821:virology; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology
chemical_list: D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine