Genomic and Dietary Aspects in Gastric Cancer Risk

Study Overview
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Brief Summary
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Gastric Cancer (GC) ranks fourth in the number of deaths worldwide and it is sixth in Italy with almost 9,000 deaths in 2020. Survival of GC is one of the lowest reported amongst major cancers, thus making prevention a central priority for its control. However there is currently a lack of evidence on gastric cancer determinants. Our study will pursue the following specific objectives: analyze dietary and lifestyle habits for GC, also infrequent ones (WP1); analyze major risk factors in rare patient subgroups (WP2); develop a Genome-wide Modelling of polygenic risk score (PRS) in GC (WP3)

Detailed Description
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The Stomach cancer Pooling project (StoP) Consortium dataset has grown to the current number of 35 studies from Europe, America, Middle East and Eastern Asia. It will be used as the cornerstone upon which the investigation on the dietary and lifestyle determinants of gastric cancer (GC) will be built. It will allow the analyses of relatively infrequent habits or exposures, genetic factors as well as to perform sufficiently powered analyses of interactions and subgroups that may present relevant heterogeneity in the etiological correlates of GC. The potential of genomics to personalize and thereby improve diagnosis, treatment, and prognosis of individuals has long been recognized, but so far evidence of the opportunity for genomics to drive prevention remains limited. Recent advances in research on Polygenic Risk Score (PRS) have created new interest about the use of genetic information in prevention of common diseases and its application to risk stratification. A long-lasting open question is whether common genetic variants used to build PRS are able to predict the risk of developing complex diseases with enough power to be used in a clinical setting. The lack of large enough dataset able to allow an unbiased PRS validation, hampered this question to be answered for many years. This study builds upon the StoP project (a consortium collecting data from about 13,500 GC cases and 32,000 controls) and the UK Biobank (480 GC cases and 338,000 controls) to develop a Polygenic Risk Score for gastric cancer.

Official Title
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Interaction of Genomic and Dietary Aspects in Gastric Cancer Risk: the Global StoP Project

Conditions
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Gastric Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients participating in studies that collaborate with the StoP Project Patient enrolled by the UK Biobank Exclusion Criteria: Age <18 years old Studies with less than 80 cases of histologically confirmed Gastric Cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| StoP Consortium + UK Biobank<br>In the PRS development 338,480 cases and controls from the UK Biobank + 3,650 cases and controls from the StoP consortium studies are going to be enrolled. Cases are defined as primary gastric carcinoma patients, with histological confirmation. Controls are selected from cancer-free patients matched with the cases. | |
| StoP Consortium<br>In the analysis on the aetiology of Gastric Cancer 13,500 cases and 32,000 controls from the StoP consortium studies will be enrolled. Cases are defined as primary gastric carcinoma patients, with histological confirmation. Controls are selected from cancer-free patients matched with the cases. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of dietary and lifestyle habits, including infrequent ones on the aetiology of gastric cancer | Analysis of the association of dietary and lifestyle habits (e.g. caroteinoids, allium plant consumption, calcium, sodium intake, pipe and cigar smoking) from survey data with gastric cancer development | The analysis will be completed in three years. Data about lifestyle and dietary habits were collected through a questionnaire at enrollment. | 
| Impact of major gastric cancer risk factors on its aetiology in rarer patients subgroups | Analysis of the association between major risk factors in subgroups of studies or in rare patient groups (e.g.: gastric cancer in young people, cancer occurring at gastric cancer) and gastric cancer | The analysis will be completed in three years. Data about lifestyle and dietary habits were collected through a questionnaire at enrollment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of a genome-wide modelling of Polygenic risk score (PRS) in gastric cancer | Construction and evaluation of a PRS and a prediction model for gastric cancer, and evaluation of the performance in a validation sample | Through study completition, three years. Blood samples were collected at the diagnosis (cases) or at the enrollment (controls) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric cancer, StoP Consortium, genomics, dietary aspects, Polygenic Risk Score, gastric cardia carcinoma, gastric neoplasm