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Understanding host-microbe-environment interactions in gastric carcinogenesis for developing strategies of primary prevention and improving therapeutic outcomes

Description: The aims are to deepen our understanding of the etiological roles of host-microbe-environment interactions for stomach cancer, and how intratumor microbiota contribute to the development of chemotherapy resistance. To achieve these aims, we will first use serum samples for measuring biomarkers of atrophic gastritis among 12,614 twin subjects. Together with available genotyping data we will perform genome wide association study to search for genetic susceptibility loci, and their interactions with environmental factors, for the development of atrophic gastritis. Second, we will create a cohort of patients with precancerous lesions in the stomach. Biosamples along with detailed questionnaire data of lifelong exposures will be collected at baseline and at repeated follow-up. Stomach microbiome, transcriptome, as well as host exome and exposome, and their interactions, will be linked to disease progression. Third, we will further collect stomach cancer and paired non-cancer adjacent tissues from 100 patients. Whole exome sequencing will be performed and mutational profiles will be linked to lifetime exposome, in order to find mutational fingerprints for carcinogens. Last, we will perform deep sequencing to characterize intratumor microbiota and explore their links with development of resistance to chemotherapy and patient survival. The research results will hopefully guide the development of cost-efficient primary, secondary and tertiary prevention strategies for stomach cancer.

Funder: Vetenskapsrådet

Amount: SEK 4,800,000

Funding type: research

Funder scheme: Project grant

Start date: 2020-01-01

End date: 2023-12-31

Investigator: Weimin Ye (lead)

Institution: Karolinska Institutet

Topic: Helicobacter pylori-related gastroenterology studies

Subfield: Gastroenterology

Field: Medicine

Domain: Health Sciences