title: Increased incidence of HFE C282Y mutations in patients with iron overload and hepatocellular carcinoma developed in non-cirrhotic liver.
abstract: OBJECTIVE
  Histological and biochemical iron overload has been reported in non-tumoral liver of most patients presenting an hepatocellular carcinoma (HCC) developed in non-cirrhotic liver (NCL). The aim of our study was to investigate HFE mutations in patients with HCC in NCL.
  
  
  METHODS
  Thirty-five patients with HCC in NCL were included either retrospectively or prospectively. Clinical data, iron and viral status, and HFE gene mutations were compared between groups with (I+, n = 19) or without histological iron overload (I-, n = 16).
  
  
  RESULTS
  Twenty per cent of patients were HBV or HCV positive. Fifty-four per cent had hepatocytic iron overload at histology. Mean hepatic iron concentration was 100.2 +/- 14.6 micromol/g in I+ versus 23.2 +/- 2.1 micromol/g in I- (p<0.001). Among the 19 I+ patients, eight mutations were found: two C282Y/C282Y, three C282Y/WT, two C282Y/H63D and one H63D/H63D. None of these mutations was found in the I- group. There was no significant difference concerning the H63D heterozygous mutation between I+ or I- patients.
  
  
  CONCLUSIONS
  In patients with HCC in NCL, HBV and HCV markers are rare (20%), and mild iron overload is frequent (54%). In patients with HCC in NCL and iron overload, C282Y mutations are frequent (36.8% of cases) and significantly increased (p<0.009) compared to HCC in NCL without iron overload; these mutations are mostly heterozygous. H63D heterozygosity is not associated with liver iron overload. Because of the small size of the series, HFE C282Y mutation should be investigated on a larger scale in patients with HCC in NCL with iron overload in order to confirm this association.
authors.affiliation: Service d'Hépato-Gastroentérologie, Hôpital Saint-André, Université Bordeaux, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Blanc
authors.forename: V
authors.initials: V
authors.lastname: De Ledinghen
authors.forename: P H
authors.initials: PH
authors.lastname: Bernard
authors.forename: H
authors.initials: H
authors.lastname: de Verneuil
authors.forename: M
authors.initials: M
authors.lastname: Winnock
authors.forename: B
authors.initials: B
authors.lastname: Le Bail
authors.forename: J
authors.initials: J
authors.lastname: Carles
authors.forename: J
authors.initials: J
authors.lastname: Saric
authors.forename: C
authors.initials: C
authors.lastname: Balabaud
authors.forename: P
authors.initials: P
authors.lastname: Bioulac-Sage
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015994:Incidence; D019190:Iron Overload / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins