title: Constitutional and functional genetics of human alcohol-related hepatocellular carcinoma.
abstract: Exploration of the constitutional genetics of hepatocellular carcinoma (HCC) has identified numerous variants associated with a higher risk of liver cancer in alcoholic cirrhotic patients. Although Genome-Wide Association studies have not been carried out in the field of alcohol-related HCC, common single nucleotide polymorphisms conferring a small increase in the risk of liver cancer risk have been identified and shown to modulate ethanol metabolism, inflammation, oxidative stress, iron or lipid metabolism. Specific patterns of gene mutations including CTNNB1, TERT, ARID1A and SMARCA2 exist in alcohol-related HCC. Moreover, a specific mutational process observed at the nucleotide level by next generation sequencing has revealed cooperation between alcohol and tobacco in the development of HCC. Combining this genetic information with epidemiological and clinical data that might define specific HCC risk classes and refine surveillance strategies needs to be assessed in large prospective cohorts of patients with alcoholic cirrhosis.
authors.affiliation: AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France.|Université Paris 13, Bobigny, France.|Inserm UMR-1162, "Functional Genetics of Solid Tumours", Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Oncoimmunology, Equipe labellisée Ligue contre le Cancer, Paris, France.
authors.forename: Pierre
authors.identifier: 0000-0003-2489-0768
authors.initials: P
authors.lastname: Nahon
authors.affiliation: AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France.|Université Paris 13, Bobigny, France.|Inserm UMR-1162, "Functional Genetics of Solid Tumours", Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Oncoimmunology, Equipe labellisée Ligue contre le Cancer, Paris, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Nault
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004268:DNA-Binding Proteins; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications*; D008113:Liver Neoplasms / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: C112476:ARID1A protein, human; C495270:CTNNB1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C084011:SMARCA2 protein, human; D014157:Transcription Factors; D051176:beta Catenin; C509186:TERT protein, human; D019098:Telomerase
keywords: alcoholic liver disease; cirrhosis; genetics; liver cancer; single nucleotide polymorphisms