| Summary: | <p>Abstract</p> <p>Background</p> <p>Although most patients with hereditary haemochromatosis have <it>HFE </it>C282Y mutations, the lifetime risk to <it>HFE </it>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 <it>HFE </it>C282Y mutation; and to estimate the penetrance of this genotype with respect to hepatocellular carcinoma in East Anglia.</p> <p>Methods</p> <p>Tissue biopsies were analysed from 144 cases of hepatocellular carcinoma for <it>HFE </it>C282Y mutations; the data produced were compared with the frequency of <it>HFE </it>mutations in a large sample of the local population. Data were also retrieved from the East Anglian Cancer Intelligence Unit to determine the annual incidence of hepatocellular carcinoma; and from appropriate life tables.</p> <p>Results</p> <p>Eight out of 144 of the cases were homozygous for the <it>HFE </it>C282Y mutation, all 8 cases were male. 6 of these 8 cases had a previous diagnosis of hereditary haemochromatosis. Male <it>HFE </it>C282Y homozygotes were more likely to be diagnosed with hepatocellular carcinoma (odds ratio [OR] = 14, 95% confidence interval [CI] = 5–37). For this population, we estimate that the penetrance of the <it>HFE </it>C282Y homozygous genotype, with respect to hepatocellular carcinoma, was between 1.31 % and 2.1% for males and was zero for females.</p> <p>Conclusion</p> <p>In this population, we found that only a very small proportion of homozygotes for the <it>HFE </it>C282Y mutation developed hepatocellular carcinoma. However, individuals with this genotype have a significantly increased risk of this rare disease relative to those who do not carry the mutations.</p>
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