Interazione tra aspetti genomici e dietetici nel rischio di cancro gastrico: il progetto internazionale StoP
Principal Investigator: Stefania Boccia, Roberta Pastorino
Short title: GenoSToP
Announcement: BANDO PRIN 2022 - 2022
Project Code: PRIN-2022A4WZFC
Start date: 16/10/2023
End date: 28/02/2026
Coordinator: Università Cattolica del Sacro Cuore
Funding body: Ministero dell'Università e della Ricerca
Link: NA
Abstract: The study “Interaction of genomic and dietary aspects in gastric cancer risk: the global StoP project (GenoStop)” aims to examine the role of diet, lifestyle, and genetic factors in the etiology of gastric cancer (GC), using data from the international Stomach Cancer Pooling (StoP) consortium. This consortium brings together numerous studies on the etiology of GC and represents the largest global dataset on this disease. The team of the present project is among the leading and founding groups of the consortium.
The project is structured into three complementary Work Packages (WP), in order to pursue three specific objectives as outlined in the original proposal:
Objective 1 (WP1) (FPG1, UNIBO): to investigate the association between GC, lifestyle, and diet. In Task 1.1, the relationship between different micronutrients, macronutrients, vitamins, and GC risk is analyzed through a two-stage analytical approach within the StoP consortium. Additionally, this objective includes the analysis of less frequently consumed foods in the diet to better understand their role in GC risk.
Objective 2 (WP2) (FPG1, UNIBO): to investigate the association between traditional risk factors and GC, including in rare populations (e.g., young patients, tumors at the gastroesophageal junction, or in non-cardia locations, etc.). In Task 2.1, an analysis of the main risk factors is conducted in study subgroups and rare patient groups using StoP consortium data. As in Task 1.1, a two-stage analytical approach is adopted. Furthermore, population-attributable risks for the main modifiable risk factors are calculated to evaluate their overall impact and to estimate the preventable fraction of GC in the young Italian population.
Objective 3 (WP3) (FPG1, FPG2): to develop and validate a predictive model using the polygenic risk score (PRS) to assess hereditary risk of developing GC specifically for the European population. The PRS is constructed during the training phase through the creation of four different PRS models, each based on different statistical significance (p-value) thresholds. These thresholds reflect the strength of association between each single nucleotide polymorphism (SNP) and GC risk. Once developed, the model undergoes validation processes to ensure accuracy and reliability in estimating genetic risk for the target population. Finally, the PRS is integrated into traditional predictive models to determine whether its inclusion can improve the discriminative accuracy of GC risk estimation.
The study has a duration of 3 years and involves the participation of two operational units based in Rome (FPG1, FPG2) and one academic unit based in Bologna (UNIBO). UNIBO serves as the international data center of the StoP Project, managing the data, incorporating new studies, and preparing a unified dataset for the consortium.