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Background. Around half of the global population is chronically infected with the stomach bacterium Helicobacter pylori, making it one of the most common chronic infections worldwide. H. pylori induces the production of reactive oxygen species, DNA damage, and accelerates the degradation of the tumor suppressor protein p53, which may lead to cancer development. In this study, we investigated the relationship between H. pylori infection and the expression of p53 in gastric mucosa in a group of patients from Jordan. Methods. In this retrospective case-control study, the epithelium of gastric glands in subjects chronically infected with H. pylori was examined for the expression of p53. Paraffin-embedded gastric biopsy samples from the archives for 50 Jordanian patients diagnosed with chronic H. pylori infection and 25 samples free of H. pylori infection and any other gastric abnormalities were selected. Samples were analyzed for the presence of H. pylori as well as p53 expression levels in the mucosa and submucosa by immunohistochemical analyses and Western blotting. Results. H. pylori was detected in the gastric tissues of infected individuals (n = 50); whereas, no H. pylori infection was detected in uninfected healthy individuals (n = 25) using immunohistochemistry. In contrast to the noninfected samples of gastric mucosa, no nuclear p53 expression was detected in the infected samples using immunohistochemistry. In addition, the levels of p53 in H. pylori-positive samples detected by Western blotting were significantly lower than those in the negative individuals. Conclusion. Our data reveal that p53 protein expression decreased in gastric mucosa of patients infected with H. pylori. The loss of this tumor suppressor may play a role in the increased risk for tumor initiation associated with H. pylori carriage.

29Background: Helicobacter pylori infection is one of the most common chronic infections 30 worldwide. Around half of the global population is chronically infected with this stomach 31 bacterium. H. pylori infection is a strong risk factor for gastric cancer development. It is well-32 established that infection of the gastric epithelium with H. pylori induces the production of reactive 33 oxygen species, DNA damage and accelerates the degradation of the tumor suppressor protein 34 p53. This p53 dysregulation induced by H. pylori infection contributes to gastric carcinogenesis 35 through complex processes including but not limited to cell proliferation and apoptosis. 36Methods: In the current study, we examined whether the epithelium of the gastric glands express 37 p53 in subjects infected, chronically, with H. pylori. Seventy-five samples from Jordanian patients 38 were analyzed for the presence of H. pylori as well as the p53 expression levels in the mucosa and 39 submucosa by immunohistochemical analyses. 40 Results: In H. pylori positive-specimens, p53-positive cells in the gastric mucosa were found 41 significantly lower than in H. pylori negative-specimens.42 Conclusion: We demonstrated that p53 expression level is downregulated in gastric mucosa of 43 patients from Jordan infected with H. pylori and this alteration may predispose individuals for 44 possible tumor initiation in individuals chronically infected with H. pylori. 45 46 47 48 49 50 51 52 Helicobacter pylori (H. pylori) is a Gram-negative, spiral-shaped, microaerophilic 53 bacterium that colonizes the human stomach (1). H. pylori infection is acquired early in life, and 54 it is the strongest identified bacterial risk factor for the development of antral gastritis, peptic ulcer 55 and gastric cancer (2). More than 4.4 billion individuals are infected globally with H. pylori in 56 2015 (3). H. pylori is classified as a group 1 carcinogen according to the International Agency for 57Research on Cancer (IARC). Infection with H. pylori is recognized as a necessary but insufficient 58 cause of gastric carcinoma (1, 4). This is due to the complex interplay between bacterial virulence 59 factors and host factors that determine the progression and chronicity of infection (4). The most 60 studied H. pylori virulence genes are located in a40kb region of DNA called cytotoxin-associated 61 gene Pathogenicity Island (cagPAI) (5). One of the most distinctive virulent gene of the cagPAI is 62 the cytotoxin-associated gene A (CagA) which is delivered into epithelial cells by cagPAI encoded 63 type IV secretion system after bacterial attachment to the host. In turn, CagA as an oncoprotein 64 can disrupt several essential signaling pathways of the host into oncogenic ones (5). 65Development of gastric cancer is anticipated to be a multistep and a multifactorial process, 66 including activation of oncogenes, inhibition of tumor suppressor genes, related to oxidative stress 67 and damage induced by pathogen (6). Creating a sequence of events starting from gastr...

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