Iron overload (IO) in HFE-related hereditary hemochromatosis is associated with increased risk of... more Iron overload (IO) in HFE-related hereditary hemochromatosis is associated with increased risk of liver cancer. This study aimed to investigate the role of other genes involved in hereditary IO among patients with hepatocellular carcinoma (HCC). Patients with HCC diagnosed in our institution were included in this prospective study. Those with ferritin levels >300μg/l (males) or >200μg/l (females) and/or transferrin saturation >50% (males) or >45% (females) had liver iron concentration (LIC) evaluated by MRI. HFE C282Y and H63D mutations were screened. Genetic analyses of genes involved in hereditary IO (HFE, HJV/HFE2, HAMP, TFR2, SLC40A1, GNPAT) were performed in patients with increased LIC. 234 patients were included; 215 (92%) had common acquired risk factors of HCC (mainly alcoholism or chronic viral hepatitis). 119 patients had abnormal iron parameters. Twelve (5.1%) were C282Y homozygotes, 3 were compound C282Y/H63D heterozygotes. LIC was measured by MRI in 100 patients. 13 patients with a LIC>70 μmol/g were enrolled for further genetic analyses: two unrelated patients bore the HAMP:c.-153C>T mutation at the heterozygous state, which is associated with increased risk of IO and severe hemochromatosis. Specific haplotypes of SLC40A1 were also studied. Additional genetic risk factors of IO were found in 18 patients (7.7%) among a large series of 234 HCC patients. Screening for IO and at-risk genotypes in the general population may help prevent occurrence of HCC. For HCC patients, screening for IO and genetic analyses may be useful for etiologic diagnosis and for family screening and prevention. This article is protected by copyright. All rights reserved.
Iron overload (IO) in HFE-related hereditary hemochromatosis is associated with increased risk of... more Iron overload (IO) in HFE-related hereditary hemochromatosis is associated with increased risk of liver cancer. This study aimed to investigate the role of other genes involved in hereditary IO among patients with hepatocellular carcinoma (HCC). Patients with HCC diagnosed in our institution were included in this prospective study. Those with ferritin levels >300μg/l (males) or >200μg/l (females) and/or transferrin saturation >50% (males) or >45% (females) had liver iron concentration (LIC) evaluated by MRI. HFE C282Y and H63D mutations were screened. Genetic analyses of genes involved in hereditary IO (HFE, HJV/HFE2, HAMP, TFR2, SLC40A1, GNPAT) were performed in patients with increased LIC. 234 patients were included; 215 (92%) had common acquired risk factors of HCC (mainly alcoholism or chronic viral hepatitis). 119 patients had abnormal iron parameters. Twelve (5.1%) were C282Y homozygotes, 3 were compound C282Y/H63D heterozygotes. LIC was measured by MRI in 100 patients. 13 patients with a LIC>70 μmol/g were enrolled for further genetic analyses: two unrelated patients bore the HAMP:c.-153C>T mutation at the heterozygous state, which is associated with increased risk of IO and severe hemochromatosis. Specific haplotypes of SLC40A1 were also studied. Additional genetic risk factors of IO were found in 18 patients (7.7%) among a large series of 234 HCC patients. Screening for IO and at-risk genotypes in the general population may help prevent occurrence of HCC. For HCC patients, screening for IO and genetic analyses may be useful for etiologic diagnosis and for family screening and prevention. This article is protected by copyright. All rights reserved.
Uploads
Papers by Severine Cunat