Haemochromatosis gene mutation in hepatocellular cancer

Willis, Gavin; Wimperis, JZ; Lonsdale, Ray; Jennings, BA

doi:10.1016/s0140-6736(05)63143-1

Cited by 23 publications

(16 citation statements)

References 4 publications

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“…It is noteworthy that two of 12 (16.6%) homozygous H63D HH patients had hepatocarcinoma. Such a high prevalence of hepatocarcinoma is not observed in classical haemochromatosis38 and a normal prevalence of the C282Y mutation has been reported in patients with hepatocarcinoma 39. In this last work the H63D mutation was not investigated.…”

Section: Discussionmentioning

confidence: 84%

Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause?

Aguilar-Martinez

Bismuth

Picot

et al. 2001

Gut

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Results-Fifty of 56 subjects had biological and/or clinical abnormalities of iron metabolism. Up to two thirds of patients (n=34) had no acquired cause of IO. Among these, 12 had a phenotypic diagnosis of HH. In the iron loaded group there was a strong prevalence of male patients. No correlation was found between the potential genetic modifiers and phenotypes. No additional mutation of HFE was identified. Conclusion-The variable phenotypes associated with H63D homozygosity do not appear to be linked to other HFE mutations, to the TFR2 Y250X mutation, or to HFE or TfR gene intragenic polymorphisms. The exact role of H63D homozygosity in IO and HH needs to be further investigated in unselected populations. (Gut 2001;48:836-842)

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Section: Discussionmentioning

confidence: 84%

Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause?

Aguilar-Martinez

Bismuth

Picot

et al. 2001

Gut

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“…[16][17][18][19] Willis and colleagues 16 reported a 7% prevalence of the C282Y homozygous mutation in patients with HCC, significantly higher than that of 0.7% expected in the normal population. It must be stressed however that this study was performed retrospectively on a limited number of patients (n=28) by extracting DNA from archived tissue samples.…”

Section: Discussionmentioning

confidence: 99%

“…This prevalence was considered to be higher than that expected in the normal population. 20 Overall, the finding of a high prevalence of HFE gene mutations in HCC patients in these four studies [16][17][18][19] should be interpreted with caution because of their methodological flaws, including retrospective nature, lack of a cirrhotic control group, and limited number of patients studied. In the present study, HFE gene mutations were assessed prospectively in a large cohort of well characterised cirrhotic patients.…”

Section: Discussionmentioning

confidence: 99%

Lack of association between HFE gene mutations and hepatocellular carcinoma in patients with cirrhosis

Boige

Castéra²,

Roux³

et al. 2003

Gut

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Background: Liver cirrhosis may lead to hepatocellular carcinoma (HCC), regardless of its cause. Genetic and/or environmental factors may modulate the risk of HCC. Mutations in the HFE gene are responsible for genetic haemochromatosis, a condition known to be associated with liver cirrhosis, HCC, or both. It has recently been suggested that the C282Y HFE gene mutation may be more frequent in patients with HCC that have developed in the non-cirrhotic liver than in the general population. Whether or not HFE gene mutations are associated with an increased risk of HCC in patients with cirrhosis is unknown. Aim: To assess the prevalence of HFE gene mutations in cirrhotic patients with and without HCC. Patients and methods: A total of 133 consecutive cirrhotic patients with HCC were prospectively studied for the presence of C282Y and H63D mutations. The control group consisted of 100 cirrhotic patients without HCC. We used restriction enzyme digestion of polymerase chain reaction amplified genomic DNA for determination of HFE genotypes. Iron loading was assessed on non-tumoral liver biopsy samples from 89 patients with HCC and 73 patients without HCC. Results: The prevalence of C282Y heterozygotes was similar in patients with and without HCC (5% v 4%, respectively; p=0.65) and did not differ from that expected in the general population. None of the HCC patients was found to be homozygous for C282Y or H63D, nor compound heterozygous. The prevalence of H63D heterozygotes was similar in patients with and without HCC (31% v 38%, respectively; p=0.25). No relation was detected between HFE genotypes and hepatic iron loading in patients with or without HCC. Conclusion: C282Y and H63D mutations do not appear to be associated with an increased risk of HCC in patients with cirrhosis.

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“…We have previously studied the penetrance of the HFE mutations with respect to haemochromatosis disease manifestations by comparing the predicted birth rate of HFE C282Y homozygotes in our study population of 500,000 with the incidence of HFE C282Y-homozygous patients diagnosed with haemochromatosis, cirrhosis [10], liver cancer [11], arthritis [12] or diabetes [13]. We showed that, in this large population, few HFE C282Y homozygotes (1.4%) were diagnosed with haemochromatosis and of the remainder few were diagnosed with liver disease (2.7% – 8%) or diabetes (0 – 1.3%).…”

Section: Introductionmentioning

confidence: 99%

Hepatocellular carcinoma and the penetrance of HFEC282Y mutations: a cross sectional study

et al. 2005

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Background: Although most patients with hereditary haemochromatosis have HFE C282Y mutations, the lifetime risk to HFE C282Y homozygotes of developing fatal diseases such as hepatocellular carcinoma is uncertain. We have carried out a cross-sectional study to determine the proportion of diagnosed hepatocellular carcinoma patients who are homozygous for the HFE C282Y mutation; and to estimate the penetrance of this genotype with respect to hepatocellular carcinoma in East Anglia.

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Haemochromatosis gene mutation in hepatocellular cancer

Cited by 23 publications

References 4 publications

Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause?

Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause?

Lack of association between HFE gene mutations and hepatocellular carcinoma in patients with cirrhosis

Hepatocellular carcinoma and the penetrance of HFEC282Y mutations: a cross sectional study

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