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Oxidative DNA Damage as a Potential Early Biomarker ofHelicobacter pylori Associated Carcinogenesis

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Pathology & Oncology Research

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 ofcagA 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 ofH. 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 ofureaseA andcagA genes ofH. pylori. The results showed the presence ofH. pylori in 106 (53 %) gastric biopsies out of 200 dyspeptic patients, including 70 (66 %) cases ofcagA + ve H. pylori. The presence ofcagA 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 ofH. Pylori-associated gastric carcinogenesis.

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Acknowledgments

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.

Author information

Authors and Affiliations

  1. Immunology and Infectious Diseases Research Laboratory, Department of Microbiology, University of Karachi, Karachi, Pakistan

    Yasir Raza, Adnan Khan, Amber Farooqui, Saeed Khan & Shahana Urooj Kazmi

  2. Department of Cellular and Molecular Medicine, College of Medicine, University of Arizona, Phoenix, AZ, USA

    Yasir Raza, Alex Facista & Carol Bernstein

  3. Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan

    Muhammad Mubarak & Javed Iqbal Kazi

  4. Department of Surgery and Medicine, Civil Hospital, Karachi, Pakistan

    Syed Shakeel Akhtar

  5. Department of Histopathology, Ziauddin University and Hospital, Karachi, Pakistan

    Javed Iqbal Kazi

  6. Division of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong, 515041, China

    Amber Farooqui

Authors
  1. Yasir Raza
  2. Adnan Khan
  3. Amber Farooqui
  4. Muhammad Mubarak
  5. Alex Facista
  6. Syed Shakeel Akhtar
  7. Saeed Khan
  8. Javed Iqbal Kazi
  9. Carol Bernstein
  10. Shahana Urooj Kazmi

Corresponding author

Correspondence toMuhammad Mubarak.

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Raza, Y., Khan, A., Farooqui, A.et al. Oxidative DNA Damage as a Potential Early Biomarker ofHelicobacter pylori Associated Carcinogenesis.Pathol. Oncol. Res.20, 839–846 (2014). https://doi.org/10.1007/s12253-014-9762-1

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