Approved Research
Impact of germline mutations on the development of liver tumors
Lay summary
Liver tumors represent a significant cause of mortality worldwide. Although several environmental factors have been identified, many affected individuals never develop these tumors suggesting a genetic susceptibility. The analysis of genetic variants (i.e. difference in DNA sequence among individuals) pre-existing in normal cells and predisposing to tumor occurrence is currently a neglected field, particularly in the case of liver disease. This project aims to identify rare and common genetic variants predisposing to liver tumors. To this aim, a comparison of the genome of large cohorts of individuals with and without liver tumors will be performed. To ensure that these results are valid, a similar analysis will be conducted in a different group of patients with the same characteristics and different individuals from the general population. This project will particularly take advantage of the genetic data generated by the UK biobank in order to provide reliable analyses at the level of the general population. This project is expected to be completed within 30 months and will advance our understanding of liver tumor development and contribute to identify patients at high risk of developing such tumors.
Scope extension:
This project which aims to identify cancer predisposing genes to liver tumors in large cohorts of patients compared to controls with liver disease and from the general populaiton. It will also provide a comprehensive study of the interactions between germline and somatic alterations in liver tumors.
In addition this project aims to identify if genetically predicted fatty liver diseases (encompassing all the genes strongly associated with fatty liver disease) are causally associated with multiple liver (e.g. liver tumor) and non-liver-related outcomes, including cardiovascular disease and chronic kidney diseases. It will reliably inspect the potential causal effect between fatty liver disease and multiple liver and non-liver-related outcomes.
Scope extension:
- This project which aims to identify cancer predisposing genes to liver tumors in large cohorts of patients compared to controls with liver disease and from the general populaiton. It will also provide a comprehensive study of the interactions between germline and somatic alterations in liver tumors. In addition this project aims to identify if genetically predicted fatty liver diseases (encompassing all the genes strongly associated with fatty liver disease) are causally associated with multiple liver (e.g. liver tumor) and non-liver-related outcomes, including cardiovascular disease and chronic kidney diseases. It will reliably inspect the potential causal effect between fatty liver disease and multiple liver and non-liver-related outcomes
- Extended Scope: To date, the contribution of the genetic background and the pathophysiological basis underlying the development of organ dysfunction in patients with chronic liver disease (CLD) remains mostly unknown. Moreover, it is essential to identify patients at an earlier stage who are at risk of developing CLD-related complications, such as renal dysfunction, in order to prevent the progression to multiorgan failure. These insights could be crucial for targeting future treatment or management strategies. The final part of the current application will be devoted to identifying common genetic variations associated with organ dysfunction and CLD-related complications, including renal, and pulmonary dysfunction, and multiorgan failure in patients with chronic liver disease.