Mutations of the HFE gene in patients with hepatocellular carcinoma

Abstract

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 ϭ 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. (Am J Gastroenterol 2003;98:442-447.

Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review

“…The association between rs1800562 and HCC has been controversial. We collected nine eligible association studies (Beckman et al 2000;Lauret et al 2002;Boige et al 2003;Cauza et al 2003;Hellerbrand et al 2003;Willis et al 2005;Ropero et al 2007;Ezzikouri et al 2008a, b;Nahon et al 2008) (including 1102 HCC cases and 3766 controls) to do the metaanalysis. By using the genetic analysis method (Thakkinstian et al 2005), we found the recessive model was most applicable to this disease.…”

“…Homozygosity for mutation (Cys282Tyr, G [ A, rs1800562) in the HFE gene is responsible for the majority of cases of typical phenotypic HH (Ellervik et al 2007). However, the relationship of this mutation and HCC was controversial among reported studies (Beckman et al 2000;Lauret et al 2002;Boige et al 2003;Cauza et al 2003;Hellerbrand et al 2003;Willis et al 2005;Ropero et al 2007;Ezzikouri et al 2008a, b;Nahon et al 2008).…”

Hepatic iron concentration does not predict response to standard and pegylated-IFN/ribavirin therapy in patients with chronic hepatitis C*1

“…Increased HIC may lead to generation of hydroxyl radicals [41], induce lipid peroxidation [42], and accelerate hepatic fibrosis [8]. Furthermore it may increase the risk for development of hepatocellular carcinoma [5,43]. Finally, iron could interfere with the antiviral and immunomodulatory effects of IFN.…”

Single nucleotide polymorphisms and risk of hepatocellular carcinoma in cirrhosis

“…Several teams have reported that the prevalence of HFE C282Y mutations was increased in patients with HCC [71,72]. However, other studies have failed to confirm these associations [73][74][75]. A recent prospective study enabled a link to be made between hepatic iron overload, HFE variations and development of HCC in alcoholic cirrhosis [39] while neither of these two factors affected the risk of liver cancer in HCV-infected cirrhotic patients.…”