Dietary iron overload in the African and hepatocellular carcinoma.
Dietary iron overload occurs commonly in parts of sub-Saharan Africa. It results from the consumption of large volumes of traditional beer that is home-brewed in iron pots or drums and consequently has a high iron content. The liver becomes iron overloaded and may develop portal fibrosis or, less often, cirrhosis. A genetic predisposition to the condition has been suggested, but no putative gene has yet been identified. Although originally believed not to cause hepatocellular carcinoma, recent case-control studies have shown African Blacks with dietary iron overload to be at increased risk for the tumour and a causal association has been confirmed in an animal model. The mechanisms of iron-induced malignant transformation are yet to be fully characterised, but the close association between cirrhosis and hepatocellular carcinoma in patients with hereditary haemochromatosis and the lesser association in those with dietary iron overload, suggests that chronic necroinflammatory hepatic disease contributes to the malignant transformation. Increased hepatic iron may, however, also be directly carcinogenic. Probable mechanisms include the generation of reactive oxygen intermediates and the resultant chronic oxidative stress that damages hepatocytes and proteins, causes lipid peroxidation, and induces strand breaks, DNA unwinding, and mutations in tumour-suppressor genes and critical DNA repair genes.
Kew
Michael C
MC
MRC/CANSA/University Molecular Hepatology Research Unit, Department of Medicine, Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa. kewmc@medicine.wits.ac.za
Asare
George A
GA
D017954:Africa South of the Sahara; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019190:Iron Overload / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism; D019266:Iron, Dietary / Q000009:adverse effects*; D015227:Lipid Peroxidation; D008103:Liver Cirrhosis / Q000150:complications* / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors
D019266:Iron, Dietary; D017382:Reactive Oxygen Species