Pathology & Oncology Research

, Volume 20, Issue 4, pp 839–846 | Cite as

Oxidative DNA Damage as a Potential Early Biomarker of Helicobacter pylori Associated Carcinogenesis

  • Yasir Raza
  • Adnan Khan
  • Amber Farooqui
  • Muhammad MubarakEmail author
  • Alex Facista
  • Syed Shakeel Akhtar
  • Saeed Khan
  • Javed Iqbal Kazi
  • Carol Bernstein
  • Shahana Urooj Kazmi


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.


Helicobacter pylori Gastritis 8-hydroxy-2′-deoxyguanosine Gastric cancer Immunohistochemistry 



We are also highly thankful to Mr. Nazim, Department of Histopathology, Zaiuddun University and Hospital, for his assistance in collecting samples. We are also highly grateful to Mrs. Nikki Kelvin for the technical revision of manuscript and Dr Saleem Iqbal for helping in statistical analysis.

Financial disclosures

Funds to conduct study were provided by HEC, Pakistan. Dr. Bernstein provided consumables and bench space at University of Arizona, USA. No other financial declarations by any of the authors.

Conflict of interest

None by any of the authors.


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Copyright information

© Arányi Lajos Foundation 2014

Authors and Affiliations

  • Yasir Raza
    • 1
    • 2
  • Adnan Khan
    • 1
  • Amber Farooqui
    • 1
    • 6
  • Muhammad Mubarak
    • 3
    Email author
  • Alex Facista
    • 2
  • Syed Shakeel Akhtar
    • 4
  • Saeed Khan
    • 1
  • Javed Iqbal Kazi
    • 3
    • 5
  • Carol Bernstein
    • 2
  • Shahana Urooj Kazmi
    • 1
  1. 1.Immunology and Infectious Diseases Research Laboratory, Department of MicrobiologyUniversity of KarachiKarachiPakistan
  2. 2.Department of Cellular and Molecular Medicine, College of MedicineUniversity of ArizonaPhoenixUSA
  3. 3.Department of HistopathologySindh Institute of Urology and TransplantationKarachiPakistan
  4. 4.Department of Surgery and MedicineCivil HospitalKarachiPakistan
  5. 5.Department of HistopathologyZiauddin University and HospitalKarachiPakistan
  6. 6.Division of Immunology, International Institute of Infection and ImmunityShantou University Medical CollegeShantouChina

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