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Procarcinogenic mechanisms of Helicobacter pylori-induced atrophic gastritis in a population of high gastric cancer risk

Global Noncommunicable Diseases Intiatives

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Folke Bernadotte Academy
Gastric cancer (GC) is the second most common cause of cancer death in the world and a global health problem of the poorest, around two thirds of the 700 000 yearly deaths in GC occur in low- and lower-middle-income countries. The main risk factors for GC are chronic infection with the bacterium Helicobacter pylori, tobacco smoking and poor dietary habits. We have found that patients suffering from atrophic gastritis (AG) and intestinal metaplasia (IM) in the corpus mucosa, two consequences of H. pylori infection and predisposing conditions for GC development, have defects in several protective systems of the stomach. These include blood clotting, cytochrome P450 genes (CYP enzymes), and DNA-repair systems. Our hypothesis is that the defects observed in AG and IM leads to loss of protection against ingested carcinogens such as tobacco smoke compounds and/or carcinogenic mold toxins, which allows development of cancer-inducing mutations in the stomach mucosa. This will be addressed by mRNA-sequencing of stomach samples. Transcriptome mutations will be detected and correlated to alterations in the mucosal defense systems. The project is dependent on a high-quality biobank of patient samples being collected in Nicaragua, a country of high risk for gastric cancer development. The results will provide important information regarding the mechanisms of GC development, which will aid development of future prophylaxis or therapy of GC in high-risk populations.. This project was identified by RTI International for their own research purposes and some fields do not align with The GO Map categories. End dates were estimated as one year after the start date. The Project Type "Research, Clinical" may not accurately describe this project's focus but was used for all RTI International's Global Noncommunicable Diseases Initiative projects added in June 2018. Specialties were not analyzed. All project funding was valued in 2015 USD.

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