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Understanding Gene ENvironment Interaction in ALcohol-related hepatocellular carcinoma

Project description

Genome and environment in alcohol-related liver cancer

Chronic alcohol consumption leads to alcohol-related liver disease (ALD), the most common cause of liver cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths in Europe. Patients with advanced alcohol-related hepatocellular carcinoma (ALD-HCC) have a poor prognosis, underscoring the importance of prevention and early detection. The EU-funded GENIAL project aims to identify genetic and environmental determinants in ALD-HCC onset. Researchers will investigate the mechanism by which specific genetic and environmental factors may promote liver carcinogenesis and how they increase the risk of individuals. By combining clinical, genomics and digital imaging data using AI, the consortium hopes to generate a predictive approach that can facilitate disease detection at an early stage.


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’.



Net EU contribution
€ 1 306 338,00
1050 Bruxelles / Brussel

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Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Activity type
Higher or Secondary Education Establishments
Total cost
€ 1 306 338,00

Participants (13)

Partners (1)