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Carriage of HFE mutations and outcome of surgical resection for hepatocellular carcinoma in cirrhotic patients
Author(s) -
Pirisi Mario,
Toniutto Pierluigi,
Uzzau Alessandro,
Fabris Carlo,
Avellini Claudio,
Scott Cathryn,
Apollonio Luca,
Beltrami Carlo A.,
Bresadola Fabrizio
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20000715)89:2<297::aid-cncr14>3.0.co;2-n
Subject(s) - medicine , hemochromatosis , hepatocellular carcinoma , gastroenterology , heterozygote advantage , hereditary hemochromatosis , hazard ratio , allele , compound heterozygosity , confidence interval , genetics , biology , gene
Abstract BACKGROUND Aggressive hepatocellular carcinoma (HCC) complicates frequently hereditary hemochromatosis, a disease for which a strong candidate gene, named HFE , has recently been identified. Patients with HCC who are heterozygotes for mutations in the HFE gene might have distinct features and a distinct disease course. METHODS The presence of the 2 mutations associated with hereditary hemochromatosis (C282Y and H63D) was sought by restriction fragment length polymorphism in 61 cirrhotic patients (46 males and 15 females) who underwent resection for HCC at a single institution. RESULTS There were 4 heterozygotes for the C282Y mutation and 6 homozygotes + 20 heterozygotes for the H63D mutation, with no compound heterozygotes. Carriage of ≥ 1 HFE mutated allele was significantly more frequent in HCC patients than in 149 control subjects (44% vs. 29%, P = 0.005). Among C282Y heterozygotes, 3 of 4 were female, compared with 12 of 57 wild‐type carriers ( P = 0.015); no gender distribution existed among patients carrying H63D alleles (6 of 26 vs. 9 of 35, P = 0.813). Survival was longer for patients with wild‐type HFE than for those with mutated HFE (67% vs. 22% at 3 years; hazard ratio = 0.42, 95% confidence interval = 0.21–0.80) ( P < 0.01). The negative effect on survival that resulted from possessing ≥ 1 HFE mutated allele was maintained even after adjustment for gender, age, presence of tumor capsule, presence of comorbid factors, Okuda stage, Edmonson grading, and number of lesions ( P = 0.01). CONCLUSIONS Testing for HFE mutations may help identify HCC patients with dismal prognoses for whom surgical resection may not represent the best treatment option. Cancer 2000;89:297–302. © 2000 American Cancer Society.