Willis Gavin, Bardsley Vicky, Fellows Ian W, Lonsdale Ray, Wimperis Jennie Z, Jennings Barbara A
Department of Molecular Genetics, Norfolk and Norwich University Hospital, Norwich, NR47UY, UK.
BMC Gastroenterol. 2005 Jun 1;5:17. doi: 10.1186/1471-230X-5-17.
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.
Tissue biopsies were analysed from 144 cases of hepatocellular carcinoma for HFE C282Y mutations; the data produced were compared with the frequency of HFE 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.
Eight out of 144 of the cases were homozygous for the HFE C282Y mutation, all 8 cases were male. 6 of these 8 cases had a previous diagnosis of hereditary haemochromatosis. Male HFE 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 HFE C282Y homozygous genotype, with respect to hepatocellular carcinoma, was between 1.31 % and 2.1% for males and was zero for females.
In this population, we found that only a very small proportion of homozygotes for the HFE 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.
尽管大多数遗传性血色素沉着症患者存在HFE C282Y突变，但HFE C282Y纯合子发生肝细胞癌等致命疾病的终生风险尚不确定。我们开展了一项横断面研究，以确定诊断为肝细胞癌的患者中HFE C282Y突变纯合子的比例；并估计该基因型在东安格利亚地区肝细胞癌方面的外显率。
对144例肝细胞癌病例的组织活检样本进行HFE C282Y突变分析；将所得数据与当地一大样本人群中的HFE突变频率进行比较。还从东安格利亚癌症情报部门获取数据，以确定肝细胞癌的年发病率；并从适当的生命表中获取数据。
144例病例中有8例为HFE C282Y突变纯合子，所有8例均为男性。这8例中的6例先前被诊断为遗传性血色素沉着症。男性HFE C282Y纯合子更有可能被诊断为肝细胞癌（优势比[OR]=14，95%置信区间[CI]=5-37）。对于该人群，我们估计HFE C282Y纯合基因型在肝细胞癌方面的外显率，男性为1.31%至2.1%，女性为零。
在该人群中，我们发现HFE C282Y突变纯合子中只有极小比例发生肝细胞癌。然而，相对于未携带该突变的个体，具有该基因型的个体患这种罕见疾病的风险显著增加。
