Germline mutations and somatic mosaicism in steatotic liver diseases and related liver carcinogenesis - PubMed
8 days ago
- #liver carcinogenesis
- #steatotic liver disease
- #genetic mutations
- Steatotic liver diseases, including metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease, affect nearly one-third of the global population and are a leading cause of cirrhosis and hepatocellular carcinoma.
- Genome-wide association studies have identified common genetic variants, with PNPLA3 I148M being the strongest genetic determinant across the disease spectrum.
- Somatic mosaicism in adult liver tissues reveals mutations in metabolic genes like FOXO1, GPAM, and CIDEB, providing adaptive advantages against lipotoxicity.
- Clonal haematopoiesis of indeterminate potential is linked to the risk of chronic liver diseases, metabolic dysfunction-associated steatohepatitis, and related liver cancer.
- Inherited and somatic variants influence hepatocellular carcinoma risk through effects on chronic liver disease progression and cancer-promoting pathways like telomere maintenance and WNT signalling.
- Polygenic risk scores show promise for risk stratification but face limitations before achieving full clinical potential.