Mutations of the HFE gene in patients with hepatocellular carcinoma

Am J Gastroenterol. 2003 Feb;98(2):442-7. doi: 10.1111/j.1572-0241.2003.07222.x.


Objective: Hepatocellular carcinoma (HCC) is a late consequence of severe liver disease. Patients with genetic hemochromatosis may be at risk for HCC, but limited information is available on the relationship of HCC and heterozygosity for the HFE gene mutations.

Methods: HFE mutations (C282Y and H63D) were assessed in 162 consecutive patients (131 men/31 women) with HCC. A total of 159 patients had cirrhosis. The most common etiologies of cirrhosis were chronic viral hepatitis (hepatitis C 39%, hepatitis B 9%) and alcoholic liver disease (36%).

Results: Five patients were C282Y homozygotes, four C282Y/H63D compound heterozygotes, and three H63D homozygotes. The C282Y and H63D allele frequencies in HCC were 8.3 (95% confidence limit = 5.3-11.3) and 11.1 (7.8-14.6), respectively, and not different from previously published data in healthy subjects or patients with chronic hepatitis C in Austria. Furthermore, there was no difference in the age at diagnosis in patients with or without HFE gene mutations. C282Y homozygotes had a 19-fold increased risk to develop HCC. In contrast, all other HFE allele constellations were not associated with such a risk.

Conclusions: Except for C282Y homozygotes, HFE gene mutations do not increase the risk to develop HCC in patients with cirrhosis.

MeSH terms

  • Arthralgia / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Female
  • Gene Frequency
  • Hemochromatosis / genetics*
  • Hemochromatosis Protein
  • Hepatitis C, Chronic / genetics
  • Heterozygote
  • Histocompatibility Antigens Class I / genetics*
  • Homozygote
  • Humans
  • Liver Cirrhosis / genetics
  • Liver Neoplasms / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Mutation, Missense*


  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins