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Understanding microbe-induced stomach cancer – the key to a workable strategy for worldwide prevention

Objective

Stomach cancer is the 4th most common cancer and 2nd leading cause of cancer-related death worldwide. The aim of this proposal is to deepen the understanding of mechanisms involved in microbe-induced gastric carcinogenesis, which will facilitate risk stratification for identification of high-risk groups and may offer new opportunities for pharmacological and probiotic prevention. We hypothesize that novel H. pylori genotypic variation can predict carcinogenicity. The cancer-causing H. pylori strains may no longer be present at the time of cancer diagnosis, displaced by a changed microenvironment and invading microorganisms. We further hypothesize that the composition of invading microorganisms determines the risk of stomach cancer. To test these hypotheses, we will perform a case-control study nested within a historic cohort of patients with gastric biopsies taken decades ago. For cases who developed stomach cancer several years after index biopsy and their matched controls, paraffin-embedded blocks will be retrieved for metagenomic analysis of H. pylori and other microfloras, using our new method with laser capture micro-dissection, DNA amplification and sequencing. Interactions of host response and environmental exposures with the gastric microbiome will also be checked. To explore the molecular mechanism underlying the gastric carcinogenesis, we will further examine gastric epigenetic changes and mutation profiles by novel methods which require minute amount of starting material. Moreover, we will develop non-invasive tests for infections with carcinogenic strains of H. pylori and other microorganisms, which can easily be deployed in low-resource countries. This project will not only contribute significantly to reducing the worldwide burden of this dreaded malignancy, but also broaden our understanding of the mechanisms linking infection, inflammation and cancer development, and open a door for research using the vast resources of archived pathology materials.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2015-CoG

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Host institution

KAROLINSKA INSTITUTET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 941 531,00
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 941 531,00

Beneficiaries (1)

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