Risk of HCC: Genetic heterogeneity and complex genetics

Hepatocellular carcinoma (HCC) is a common form of cancer that arises from hepatocytes and whose risk may be affected by several known environmental factors, including hepatitis viruses, alcohol, cigarette smoking, and others. Rare monogenic syndromes, such as alpha1-antitrypsin deficiency, glycogen storage disease type I, hemochromatosis, acute intermittent and cutanea tarda porphyria, as well as hereditary tyrosinemia type I are associated with a high risk of HCC. Several common conditions or diseases inherited as polygenic traits e.g. autoimmune hepatitis, type 2 diabetes, a family history of HCC, hypothyroidism, and non-alcoholic steatohepatitis also show an increased risk of HCC compared to the general population. Overall, the genetic susceptibility to HCC is characterized by a genetic heterogeneity; a high individual risk of HCC may thus be caused by several unlinked single gene defects, whose carriers are rare in the general population, or by more common conditions inherited by complex genetics.

Abbreviations: HCC, hepatocellular carcinoma, HBV, hepatitis B virus, HCV, hepatitis C virus, AAT, alpha1-antitrypsin, OR, odds ratio, AIP, acute intermittent hepatic porphyria, PCT, porphyria cutanea tarda, AIH, autoimmune hepatitis, HLA, human leukocyte antigen, IGF, insulin-like growth factor, GWAS, genome-wide association studies, HBsAg, HBV surface antigen, NASH, non-alcoholic steatohepatitis, AFB1, aflatoxin B1, GST, glutathione S-transferase, Hcs, hepatocarcinogenesis susceptibility, Hcr, hepatocarcinogenesis resistance

Keywords: Cirrhosis, Glycogen storage disease, Hemochromatosis, Hepatitis, Non-alcoholic steatohepatitis, Porphyrias, Tyrosinemia type I