Hepatocellular carcinoma and the penetrance of HFE C282Y mutations: a cross sectional study
نویسندگان
چکیده
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. METHODS 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. RESULTS 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. CONCLUSION 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.
منابع مشابه
Willis, Hepatocellular carcinoma and HFE mutations Hepatocellular carcinoma and the penetrance of HFE C282Y mutations: a cross sectional study
متن کامل
Frequency of C282Y and H63D Mutations of HFE Gene and Their Correlation with Iron Status in Iranian Beta-Thalassemia Major Patients
Background: Co-inheritance of hemochromatosis (HFE) gene mutations may play an essential role in the pathogenesis of iron overload in beta-thalassemia major (BTM) patients. The present study aimed to investigate the prevalence of HFE C282Y and H63D mutations in BTM patients and their correlation with some demographic data and biochemical iron markers. Materials and Methods: The study populat...
متن کاملموتاسیونهای HFE در بیماران ایرانی مبتلا به هپاتیت ب
Background : Finding an association between HFE mutations and hepatitis C especially in those with iron overload is the focus of recent researches. We examined the frequency of these mutations and ferritin level in a group of patients with different stages of hepatitis B and healthy individuals. Materials and methods : A total of 75 (18 carrier, 57 chronic) cases of HBsAg positive patients and...
متن کاملPrevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States.
CONTEXT Population-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening. OBJECTIVE To estimate the prevalence of the HFE mutations C282Y and H63D in the US population. DESIGN Cross-sectional population-based study of samples in the DNA bank from phase 2 of the Third Nation...
متن کاملAnalysis of haemochromatosis gene mutations in a population from the Mediterranean Basin.
BACKGROUND/AIMS The C282Y mutation in the haemochromatosis gene (HFE) located on chromosome 6 has been identified as the main genetic basis of hereditary haemochromatosis (HH). Two more mutations of that gene, H63D and S65C, appear to be associated with milder forms of HH. A high allele frequency for C282Y and H63D mutations was reported in populations from North Europe, while incomplete inform...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- BMC Gastroenterology
دوره 5 شماره
صفحات -
تاریخ انتشار 2005