铁超载与肝细胞癌关系的研究进展

赵睿; 张岭漪

铁超载与肝细胞癌关系的研究进展

赵睿,
张岭漪

兰州大学第二医院肝病科甘肃省消化系肿瘤重点实验室

基金项目:

甘肃省自然科学基金(1010RJZA087)；

详细信息

中图分类号: R735.7
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出版历程
- 出版日期: 2011-06-20

Recent progress in relationship between iron overload and hepatocellular carcinoma

Research funding:

摘要

摘要: 肝细胞癌(HCC)的发生与多种因素有关。早期的流行病学研究显示非洲人群饮食中铁过量与HCC发生相关,继而研究发现许多与铁沉积相关的疾病如遗传性血色素沉积症(HH)、丙型病毒性肝炎、非酒精性脂肪性肝病(NAFLD)等在发展过程中均有发生HCC的可能性,提示铁超载可能在其中发挥着直接或间接的作用。现认为铁超载的发生与基因突变、铁代谢相关基因蛋白的异常表达、氧化应激反应、免疫紊乱、促进癌细胞生长等因素有关。本文就铁超载与HCC的相关研究现状作一综述。
- 肝肿瘤 /
- 铁
Abstract: Hepatocellular carcinoma (HCC) is associated with many specific etiologies.Some epidemiological investigations has shown that dietary iron overload is associated with HCC in Africans.And subsequent studies found that many iron-loading diseases, such as hereditary hemochromatosis, chronic hepatitis C, nonalcoholic fatty liver disease etc, appeared to increase the risk of HCC with the development of these diseases.The carcinogenic potential of these iron-loading diseases is probably mainly associated with genetic mutation, abnormal expression of iron metabolism related proteins, oxidative stress reaction, immune disorder and so on.We summarized the recent findings concerning the correlation between iron-loading diseases and HCC.
- liver neoplasms /
- iron

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参考文献(27)

[1]Gordeuk VR, McLaren CE, MacPhail AP, et al.Associationsof iron overload in Africa and hepatocellular carcinoma andtuberculosis[J].Blood, 1996, 87 (8) :3470-3476.

[2]Mandishoma E, MacPhail AP, Gordeuk VR, et al.Dietary ironoverload as a risk factor for hepatocellular carcinoma in BlackAfricans[J].Hepatology, 1998, 27 (6) :1563-1566.

[3]Asare GA, Paterson AC, Kew MC, et al.Iron-free neoplasticnodules and hepatocellular carcinoma without cirrhosis in Wistarrats fed a diet high in iron[J].Pathol, 2006, 208 (1) :82-90.

[4]Sorrentino P, D'Angelo S, Ferbo U, et al.Liver iron excess in patients with hepatocellular carcinoma developed on non-alcoholicsteato-hepatitis[J].Hepatology, 2009, 50 (2) :351-357.

[5]Elmberg M, Hultcrantz R, Ekbom A, et al.Cancer risk in patientswith hereditary hemochromatosis and in their first-degreerelatives[J].Gastroenterology, 2003, 25 (6) :1733-1741.

[6]Kowdley KV.Iron, hemochromatosis, and hepatocellularcarcinoma[J].Gastroenterology, 2004, 127 (5) :S79-S86.

[7]Pelisse M, Gonzalez-Abraldes J, Navasa M, et al.Hepatocellul-ar carcinoma in a patient with Hereditary hemochromatosiswithout cirrhosis[J].Hepatology, 2001, 24 (3) :132-134.

[8]Asare GA, Mossanda KS, Kew MC, et al.Hepatocellularcarcinoma caused by iron overload:a possible mechanism ofdirect hepatocarcinogenicity[J].Toxicology, 2006, 219 (1-3) :41-52.

[9]Blanc JF, De Ledinghen V, Bernard PH, et al.Increasedincidence of HFE C282Y mutations in patients with iron overloadand hepatocellular carcinoma developed in non-cirrhoticliver[J].Hepatology, 2000, 32 (5) :805-811.

[10]Kearney SL, Nemeth E, Neufeld EJ, et al.Urinary hepcidin incongenital chronic anemias[J].Pediatr Blood Cancer, 2007, 48 (1) :57-63.

[11]Bioge V, Castera L, de Roux N, et al.Lack of associationbetween HFE gene mutations and hepatocellular carcinoma inpatients with cirrhosis[J].Gut, 2003, 52 (8) :1178-1181.

[12]Weinstein DA, Roy CN, Fleming MD, et al.Inappropriateexpression of hepcidin is associated with iron refractoryanemia:implication for the anemia of chronic disrease[J].Blood, 2002, 100 (10) :3776-3781.

[13]Macedo MF, Porto G, Costa M, et al.Low numbers of CD8+Tlymphocytes in hereditary haem-ochromatosis are explainedby a decrease of the most mature CD8+effector memory T cells[J].Clin Exp Immunol, 2010, 159 (3) :363-371.

[14]Ohata K, Hamasaki K, Toriyama K, et al.Hepatic steatosis is arisk factor for hepatocellular carcinoma in patients with chronichepatitis C virus infection[J].Cancer, 2003, 97 (12) :3036-3043.

[15]Nishina S, Korenaga M, Hidaka I, et al.Hepatitis C virus proteinand iron overload induce hepatic steatosis through the unfoldprotein response in mice[J].Liver international, 2010, 30 (5) :683-692.

[16]Nishina S, Hino K, Korenaga M, et al.Hepatitis C virus-inducedreactive oxygen species raise hepatic iron level in mice byreducing hepcidin transcription[J].Gastroenterology, 2008, 134 (1) :226-238.

[17]Furutani T, Hino K, Okuda M, et al.Hepatic iron overload induces hepatocelluar carcinoma in transgenic mice expressingthe hepatitis C virus polyprotein[J].Gastroenterology, 2006, 130 (7) :2087-2098.

[18]Marroqi AJ, Khan MA, van Gijssel HE, et al.Oxidative stressand p53 mutations in the carcinogenesis of iron-overload-associated hepatocellular carcinoma[J].Natl Cancer Inst, 2001, 93 (21) :1652-1655.

[19]Blumberg RS, Chopra S, Ibrahim R, et al.Primary hepatocellularcarcinoma in idiopathic hemoehromatosis after reversalcirrhosis[J].Gastroenterology, 1988, 95 (5) :1399-1402.

[20]Kohgo Y, Ohtake T, Ikuta K, et al.Iron accumulation in alcoholicliver diseases[J].Alcohol, 2005, 29 (11 Suppl) :189S-193S.

[21]Takada A, Takase S, Tsutsumi M.Characteristic features ofalcoholic liver disease in Japan:a review[J].Gastroenterol Jpn, 1993, 28 (1) :137-148.

[22]Pinto JP, Ribeiro S, Pontes H, et al.Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling andregulation of C/EBPalpha[J].Blood, 2008, 111 (12) :5727-5733.

[23]Fleming RE, Sly WS.Hepcidin:a putative iron-regulatoryhormone relevant to hereditary hemochromatosis and theanemia of chronic disease[J].Proc Natl Acad U S A, 2001, 98 (15) :8160-8162.

[24]Sutton A, Nahon P, Pessayre D, et al.Genetic polymorphisms inantioxidant enzymes modulate hepatic iron accumulation andhepatocellular carcinoma development in patients with alcohol-induced cirrhosis[J].Cancer, 2006, 66 (5) :2844-2852.

[25]Vecchi C, Montosi G, Zhang K, et al.ER stress controls ironmetabolism through induction of hepcidin[J].Science, 2009, 325 (5942) :877-880.

[26]武荣兰, 封顺, 王吉德, 等.黄苓苷及其金属配合物的抗氧性研究[J].科技导报, 2005, 24 (1) :36-37.

[27]Popovic Z, Templeton DM.Iron accumulation and iron-regulatory protein activity in human hepatoma (HepG2) cells[J].Mol Cell Biochem, 2004, 265 (1-2) :37-45.

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