Periodic Reporting for period 4 - PreventStoCan (Understanding microbe-induced stomach cancer – the key to a workable strategy for worldwide prevention)
Période du rapport: 2021-01-01 au 2022-06-30
Stomach cancer is the 4th most common cancer and 2nd leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is the single most important risk factor for stomach cancer. Although theoretically population-based widespread eradication of the bacterium can reduce stomach cancer incidence and mortality, the concerns of inducing multidrug resistance problems and iatrogenic diseases related to Helicobacter pylori eradication, have hampered the implementation of this approach. We aim to develop a cost-effective and safe program for stomach cancer prevention through identification of high-risk groups, on which chemoprevention or endoscopic screening can be targeted. Taking advantage of unique setting in Sweden for epidemiological studies, in combination with the development of modern molecular biological techniques, we have created a database comprising of metagenomics, mutation and methylation profile, and biomarkers of DNA damage, stem cells and inflammation, from tissue blocks years before stomach cancer occurrence. By comparison to matched controls, this database will help to improve our previously established stomach cancer prediction model.
We created a cohort from Swedish computerized pathology registers, comprising of patients who underwent endoscopic examination with stomach biopsy between 1979 and 2014. This cohort was linked to Cancer Register and other health and demographic registers to identify stomach cancer cases and to obtain necessary information for censoring. We then conducted two nested case-control studies, among subjects with non-atrophic gastritis and atrophic gastritis (or more severe lesions), respectively. For paired stomach cancer cases and controls, formalin-fixed paraffin-embedded tissue blocks from baseline endoscopy were retrieved. We developed various methods for constructing Helicobacter pylori genome, metagenomics analysis, identification of mutation and methylation profile, and assaying biomarkers of DNA damage, stem cells and inflammation, which are tailored for long-term archived tissue blocks. We applied these technologies to the archived tissue samples, and created a unique database enabling us to understand gastric carcinogenesis and identify risk stratification markers. Besides, we developed a loop-mediated isothermal amplification assay for Helicobacter pylori detection using non-invasive and self-sampling methods, which are suitable in low-resources populations. We have also used a population-based case-control study to create a stomach cancer risk prediction model, which awaits to be further developed. Results from our paper have been adopted in updated guideline for management of patients with gastric lesions by Swedish Gastroenterological Association, and presented in several seminars.
Our project has taken advantage of unique setting in Sweden for epidemiological studies. In combination with our dedicated methodological development for long-term archived FFPE tissue blocks, we have created a database containing Helicobacter pylori whole genome and other metagenome, along with molecular changes many years before stomach cancer occurrence. By comparison with matched cancer-free controls, our results will hopefully deepen the understanding of the mechanisms involved in microbe-induced gastric carcinogenesis.