Description du projet
Génome et environnement dans le cancer du foie lié à l’alcool
La consommation chronique d’alcool entraîne une maladie hépatique liée à l’alcool (ALD), qui est la cause la plus fréquente de cirrhose du foie, de carcinome hépatocellulaire (CHC) et de décès liés au foie en Europe. Le pronostic des patients atteints d’un carcinome hépatocellulaire lié à l’alcool à un stade avancé (ALD-HCC) est sombre, ce qui souligne l’importance de la prévention et de la détection précoce. Le projet GENIAL, financé par l’UE, se propose d’identifier les déterminants génétiques et environnementaux de l’apparition de l’ALD-HCC. Les chercheurs étudieront le mécanisme par lequel des facteurs génétiques et environnementaux spécifiques peuvent favoriser la carcinogenèse du foie et comment ils augmentent le risque pour les individus. En combinant les données cliniques, génomiques et d’imagerie numérique à l’aide de l’IA, le consortium espère générer une approche prédictive susceptible de faciliter la détection de la maladie à un stade précoce.
Objectif
Alcohol-related hepatocellular carcinoma (ALD-HCC) is, in Europe, the leading cause of liver cancer (2nd most common cause of cancer-related death worldwide, affecting both men and women). ALD-HCC has a median 5-year survival rate of 15%. Yet, the prognosis is driven by the tumour stage, with curative options providing a 5-year survival exceeding 70% for early-stage HCC (<20% of cases). Therefore, interventions aiming to improve prevention and early detection are key. ALD-HCC results from the interplay between environmental determinants and genetic variations. A comprehensive characterisation of environmental factors (e.g. diet, lifestyle) linked to ALD-HCC is still lacking. We recently performed the 1st genome-wide association study of ALD-HCC and identified predisposing genetic variations. However, their role on alcohol-related liver carcinogenesis needs clarification and the genetic architecture of ALD-HCC remains mostly unknown. GENIAL brings together partners with unique expertise in clinical hepatology, single-cell and spatial multi-omics, artificial intelligence (AI) and communication and dissemination capacities. Our aim is to 1) portray genetic and environmental determinants promoting ALD-HCC; 2) evaluate how they interact at cellular level in human samples and preclinical models to get novel insights into liver carcinogenesis, and identify chemopreventive targets; and 3) assess how these determinants modulate the ALD-HCC risk in prospective cohorts of patients included in HCC surveillance programs. Environmental factors will be comprehensively characterised in an ongoing clinical trial designed to evaluate alternative methods for early-stage HCC detection. Finally, AI models, reaching the minimal viable product stage by the end of GENIAL, will be used to integrate genetic and non-genetic information (including digital imaging) to develop novel cost-effective strategies towards prevention and early-stage detection of ALD-HCC in at-risk individuals.
This action is part of the Cancer Mission cluster of projects on ‘‘Understanding’.
Champ scientifique
Programme(s)
- HORIZON.2.1 - Health Main Programme
Régime de financement
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinateur
1050 Bruxelles / Brussel
Belgique