Risk of HCC: Genetic heterogeneity and complex genetics

Common mechanism by which several monogenic syndromes, whose causative gene mutations and chromosome positions are indicated, as well as several conditions under polygenic control, increase the risk of HCC. The single genetic defects and the polygenic conditions cause liver damage and necrosis, resulting in liver cirrhosis that favors accumulation and/or promotion of somatic mutations and of genetic damage and thus representing the ultimate risk factor for HCC.

Proposed model of individual susceptibility to HCC. In the general population, individuals carrying rare syndromes or a combination of susceptibility alleles (polygenic conditions) are at high genetic risk of HCC. The different colors indicate different genetic conditions providing high susceptibility to HCC, thus depicting a model characterized by genetic heterogeneity (Left). Individuals, either genetically susceptible or not, may be exposed to environmental risk factors for HCC (e.g., hepatitis virus infections, high alcohol consumption) that may induce or favor HCC development (Right). Alternatively, some genetic syndromes may cause HCC development in the absence of environmental risk factors and the latter may cause HCC by themselves.