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The role of genetic factors in patients with hepatocellular carcinoma and iron overload – a prospective series of 234 patients
Author(s) -
Funakoshi Natalie,
Chaze Iphigénie,
Alary AnneSophie,
Tachon Gaëlle,
Cunat Séverine,
GiansilyBlaizot Muriel,
Bismuth Michael,
Larrey Dominique,
Pageaux GeorgesPhilippe,
Schved JeanFrançois,
DonnadieuRigole Hélène,
Blanc Pierre,
AguilarMartinez Patricia
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12984
Subject(s) - hepatocellular carcinoma , medicine , gastroenterology , hemochromatosis , transferrin saturation , hereditary hemochromatosis , prospective cohort study , liver cancer , genotype , ferritin , gene , genetics , serum ferritin , biology
Background & Aims Iron overload ( IO ) in HFE ‐related hereditary haemochromatosis 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 ). Methods Patients with HCC diagnosed in our institution were included in this prospective study. Those with ferritin levels ≥300 μg/L (males) or ≥200 μg/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 / HFE 2, HAMP , TFR 2, SLC 40A1, GNPAT ) were performed in patients with increased LIC . Results A total of 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, three were compound C282Y/H63D heterozygotes. LIC was measured by MRI in 100 patients. Thirteen patients with a LIC >70 μmol/g were enrolled in 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 haemochromatosis. Specific haplotypes of SLC 40A1 were also studied. Conclusions 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 the associated at‐risk genotypes in patients who have developed HCC, is useful for both determining etiologic diagnosis and enabling family screening and possibly primary prevention in relatives.