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Trace Element Concentration in Primary Liver Cancers—A Systematic Review

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Abstract

Background

The incidence of primary liver cancer varies between countries. Many of the etiological factors contributing to the geographical variations in incidence are unknown. Development of hepatocellular carcinoma has been linked to levels of trace elements. This review summarizes the evidence associating HCC with trace elements.

Methods

MEDLINE, EMBASE, and CENTRAL databases were searched. Various inclusion and exclusion criteria were applied to select the articles for inclusion. Data extraction was performed using a custom designed data extraction form.

Results

A total of 12,344 references were identified. Duplicates, 1,597, were excluded. Clearly irrelevant references, 10,676, were excluded through reading titles and abstracts. Some references (59) were excluded by applying the exclusion criteria. Twelve studies including 646 patients and measuring iron content (8), copper content (11), zinc (9), and selenium (2) qualified for the review. Although a meta-analysis was not possible due to heterogeneity between the studies, a clear pattern of distribution of the trace elements was discernible.

Conclusion

Iron and zinc content are lower in HCC than in surrounding tissues or normal controls. Copper content is lower in HCC than in surrounding tissues and cirrhotic controls. Epidemiological and physiological reasons for the trace element alterations should be further investigated.

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References

  1. National statistics (2005) Cancer Statistics Registrations. Registrations of cancer diagnosed in 2002. Series MBI no.33

  2. International Agency for Research on Cancer. CANCER Mondial Statistical information system. GLOBOCAN 2002 database: summary table by cancer

  3. Ikai I, Arii S, Ichida T, Okita K, Omata M, Kojiro M, Takayasu K, Nakanuma Y, Makuuchi M, Matsuyama Y, Yamaoka Y (2005) Report of the 16th follow-up survey of primary liver cancer. Hepatol Res 32:163–172

    Article  PubMed  Google Scholar 

  4. Yuan SF, Li KZ, Wang L, Dou KF, Yan Z, Han W, Zhang YQ (2005) Expression of MUC1 and its significance in hepatocellular and cholangiocarcinoma tissue. World J Gastroenterol 11:4661–4666

    PubMed  CAS  Google Scholar 

  5. Thomas MB, Zhu AX (2005) Hepatocellular carcinoma: the need for progress. J Clin Oncol 23:2892–2899

    Article  PubMed  Google Scholar 

  6. Kaczynski J, Hansson G, Wallerstedt S (2005) Clinical features in hepatocellular carcinoma and the impact of autopsy on diagnosis. A study of 530 cases from a low-endemicity area. Hepato-gastroenterol 52:1798–1802

    Google Scholar 

  7. Kubicka S, Rudolph KL, Hanke M, Tietze MK, Tillmann HL, Trautwein C, Manns M (2000) Hepatocellular carcinoma in Germany: a retrospective epidemiological from a low-endemic area. Liver 20:312–318

    Article  PubMed  CAS  Google Scholar 

  8. Hellerbrand C, Hartmann A, Richter G, Knoll A, Wiest R, Scholmerich J, Lock G (2001) Hepatocellular carcinoma in southern Germany: epidemiological and clinicopathological characteristics and risk factors. Dig Dis 19:345–351

    Article  PubMed  CAS  Google Scholar 

  9. Brotodihardjo AE, Tait N, Weltman MD, Liddle C, Little JM, Farrell GC (1994) Hepatocellular carcinoma in western Sydney. Aetiology, changes in incidence, and opportunities for better outcomes. Med J Aust 161:433–435

    PubMed  CAS  Google Scholar 

  10. Gheorghe L, Iacob S, Simionov I, Vadan R, Gheorghe C, Iacob R, Parvulescu I, Constantinescu I (2005) Natural history of compensated viral B and D cirrhosis. Rom J Gastroenterol 14:329–335

    PubMed  Google Scholar 

  11. Benvegnu L, Gios M, Boccato S, Alberti A (2004) Natural history of compensated viral cirrhosis: a prospective study on incidence and hierarchy of major complications. Gut 53:744–749

    Article  PubMed  CAS  Google Scholar 

  12. Planas R, Balleste B, Alvarez MA, Rivera M, Montoliu S, Galeras JA, Santos J, Coll S, Morillas RM, Sola R (2004) Natural history of decompensated hepatitis C virus-related cirrhosis. Study of 200 patients. J Hepatol 40:823–830

    Article  PubMed  Google Scholar 

  13. Kim YS, Um SH, Ryu HS, Lee JB, Lee JW, Park DK, Kim YS, Jin YT, Chun HJ, Lee HS, Lee SW, Choi JH, Kim CD, Hyun JH (2003) The prognosis of liver cirrhosis in recent years in Korea. J Korean Med Sci 18:833–841

    Article  PubMed  Google Scholar 

  14. Gentilini P, Laffi G, La Villa G, Romanelli RG, Buzzelli G, Casini-Raggi V, Melani L, Mazzanti R, Riccardi D, Pinzani M, Zignego AL (1997) Long course and prognostic factors of virus-induced cirrhosis of the liver. Am J Gastroenterol 92:66–72

    PubMed  CAS  Google Scholar 

  15. Ryder SD (2003) Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults. Gut 52(Suppl 3):iii1–iii8

    PubMed  Google Scholar 

  16. Ou C, Wu FX, Luo Y, Cao J, Zhao YN, Yuan WP, Li Y, Su JJ (2005) Expression and significance of epidermal growth factor receptor variant type III in hepatocellular carcinoma. Ai Zheng 24:166–169 [English Abstract]

    PubMed  CAS  Google Scholar 

  17. Zeng ZJ, Yang LY, Ding X, Wang W (2004) Expressions of cysteine-rich61, connective tissue growth factor and Nov genes in hepatocellular carcinoma and their clinical significance. World J Gastroenterol 10:3414–3418

    PubMed  CAS  Google Scholar 

  18. Dong ZZ, Yao DF, Yao DB, Wu XH, Wu W, Qiu LW, Jiang DR, Zhu JH, Meng XY (2005) Expression and alteration of insulin-like growth factor II-messenger RNA in hepatoma tissues and peripheral blood of patients with hepatocellular carcinoma. World J Gastroenterol 11:4655–4660

    PubMed  CAS  Google Scholar 

  19. Jiang Y, Zhou XD, Liu YK, Wu X, Huang XW (2002) Association of hTcf-4 gene expression and mutation with clinicopathological characteristics of hepatocellular carcinoma. World J Gastroenterol 8:804–807

    PubMed  CAS  Google Scholar 

  20. Zhao H, Rui J, Cong X, Zhao Y, Wang S, Chen S, Wang Y, Wang Y, Leng X, Chen W (2002) Expression and clinical significance of MAGE-4 gene in human hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi 10:100–102 [English Abstract]

    PubMed  CAS  Google Scholar 

  21. Moon WS, Chang KJ, Majumdar AP, Tarnawski AS (2004) Reduced expression of epidermal growth factor receptor-related protein in hepatocellular carcinoma: implications for cancer growth. Digestion 69:219–224

    Article  PubMed  CAS  Google Scholar 

  22. Huang GW, Yang LY (2002) Metallothionein expression in hepatocellular carcinoma. World J Gastroenterol 8:650–653

    PubMed  CAS  Google Scholar 

  23. Sun BH, Zhao XP, Wang BJ, Yang DL, Hao LJ (2000) FADD and TRADD expression and apoptosis in primary hepatocellular carcinoma. World J Gastroenterol 6:223–227

    PubMed  CAS  Google Scholar 

  24. Hu TH, Huang CC, Lin PR, Chang HW, Ger LP, Lin YW, Changchien CS, Lee CM, Tai MH (2003) Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer 97:1929–1940

    Article  PubMed  CAS  Google Scholar 

  25. Wan XW, Jiang M, Cao HF, He YQ, Liu SQ, Qiu XH, Wu MC, Wang HY (2003) The alteration of PTEN tumor suppressor expression and its association with the histopathological features of human primary hepatocellular carcinoma. J Cancer Res Clin Oncol 129:100–106

    PubMed  CAS  Google Scholar 

  26. Haddow JE, Palomaki GE, McClain M, Craig W (2003) Hereditary haemochromatosis and hepatocellular carcinoma in males: a strategy for estimating the potential for primary prevention. J Med Screen 10:11–13

    Article  PubMed  CAS  Google Scholar 

  27. Elmberg M, Hultcrantz R, Ekbom A, Brandt L, Olsson S, Olsson R, Lindgren S, Loof L, Stal P, Wallerstedt S, Almer S, Sandberg-Gertzen H, Askling J (2003) Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. Gastroenterology 125:1733–1741

    Article  PubMed  Google Scholar 

  28. Bradbear RA, Bain C, Siskind V, Schofield FD, Webb S, Axelsen EM, Halliday JW, Bassett ML, Powell LW (1985) Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver diseases. J Natl Cancer Inst 75:81–84

    PubMed  CAS  Google Scholar 

  29. Niederau C, Fischer R, Sonnenberg A, Stremmel W, Trampisch HJ, Strohmeyer G (1985) Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N Engl J Med 313:1256–1262

    Article  PubMed  CAS  Google Scholar 

  30. Mandishona E, MacPhail AP, Gordeuk VR, Kedda MA, Paterson AC, Rouault TA, Kew MC (1998) Dietary iron overload as a risk factor for hepatocellular carcinoma in Black Africans. Hepatology 27:1563–1566

    Article  PubMed  CAS  Google Scholar 

  31. Britto MR, Thomas LA, Balaratnam N, Griffiths AP, Duane PD (2000) Hepatocellular carcinoma arising in non-cirrhotic liver in genetic haemochromatosis. Scand J Gastroenterol 35:889–893

    Article  PubMed  CAS  Google Scholar 

  32. Goh J, Callagy G, McEntee G, O’Keane JC, Bomford A, Crowe J (1999) Hepatocellular carcinoma arising in the absence of cirrhosis in genetic haemochromatosis: three case reports and review of literature. Eur J Gastroenterol Hepatol 11:915–919

    Article  PubMed  CAS  Google Scholar 

  33. Thompson NP, Stansby G, Jarmulowicz M, Hobbs KE, McIntyre N (1995) Hepatocellular carcinoma arising in non-cirrhotic haemochromatosis. HPB Surg 8:163–166

    PubMed  CAS  Google Scholar 

  34. Tomao S, Romiti A, Mozzicafreddo A, Raffaele M, Zullo A, Antonaci A (1998) Onset of hepatocellular carcinoma in a non-cirrhotic patient affected with haemochromatosis. Oncol Rep 5:723–725

    PubMed  CAS  Google Scholar 

  35. Fellows IW, Stewart M, Jeffcoate WJ, Smith PG, Toghill PJ (1988) Hepatocellular carcinoma in primary haemochromatosis in the absence of cirrhosis. Gut 29:1603–1606

    PubMed  CAS  Google Scholar 

  36. Kohler HH, Hohler T, Kusel U, Kirkpatrick CJ, Schirmacher P (1999) Hepatocellular carcinoma in a patient with hereditary hemochromatosis and noncirrhotic liver. A case report. Pathol Res Pract 195:509–513

    PubMed  CAS  Google Scholar 

  37. Barbouti A, Doulias PT, Zhu BZ, Frei B, Galaris D (2001) Intracellular iron, but not copper, plays a critical role in hydrogen peroxide-induced DNA damage. Free Radic Biol Med 31:490–498

    Article  PubMed  CAS  Google Scholar 

  38. Asare GA, Mossanda KS, Kew MC, Paterson AC, Kahler-Venter CP, Siziba K (2005) Hepatocellular carcinoma caused by iron overload: a possible mechanism of direct hepatocarcinogenicity. Toxicology 219:41–52

    Article  PubMed  CAS  Google Scholar 

  39. Rezazadeh H, Nayebi AR, Garjani A, Sheikhulislami A, Babaei H (2005) Evidence that iron overload plus croton oil induce skin tumours in mice. Hum Exp Toxicol 24:409–413

    Article  PubMed  CAS  Google Scholar 

  40. Rezazadeh H, Athar M (1997) Evidence that iron-overload promotes 7,12-dimethylbenz(a)anthracene-induced skin tumorigenesis in mice. Redox Rep 3:303–309

    PubMed  CAS  Google Scholar 

  41. Rezazadeh H, Athar M (1998) Effect of iron overload on the benzoyl peroxide-mediated tumor promotion in mouse skin. Cancer Lett 126:135–142

    Article  PubMed  CAS  Google Scholar 

  42. Bhasin G, Kausar H, Sarwar Alam M, Athar M (2003) Progressive iron overload enhances chemically mediated tumor promotion in murine skin. Arch Biochem Biophys 409:262–273

    Article  PubMed  CAS  Google Scholar 

  43. Rakba N, Loyer P, Gilot D, Delcros JG, Glaise D, Baret P, Pierre JL, Brissot P, Lescoat G (2000) Antiproliferative and apoptotic effects of O-Trensox, a new synthetic iron chelator, on differentiated human hepatoma cell lines. Carcinogenesis 21:943–951

    Article  PubMed  CAS  Google Scholar 

  44. Kicic A, Chua AC, Baker E (2002) Desferrithiocin is a more potent antineoplastic agent than desferrioxamine. Br J Pharmacol 135:1393–1402

    Article  PubMed  CAS  Google Scholar 

  45. Chenoufi N, Drenou B, Loreal O, Pigeon C, Brissot P, Lescoat G (1998) Antiproliferative effect of deferiprone on the Hep G2 cell line. Biochem Pharmacol 56:431–437

    Article  PubMed  CAS  Google Scholar 

  46. Kim DY, Kim WH, Kang JK, Park S, Kwon OH (1994) The mechanism of antiproliferative effect of desferrioxamine on human hepatoma cell lines. Yonsei Med J 35:62–71

    PubMed  CAS  Google Scholar 

  47. Moyo VM, Makunike R, Gangaidzo IT, Gordeuk VR, McLaren CE, Khumalo H, Saungweme T, Rouault T, Kiire CF (1998) African iron overload and hepatocellular carcinoma (HA-7-0-080). Eur J Haematol 60:28–34

    Article  PubMed  CAS  Google Scholar 

  48. Chapoutot C, Esslimani M, Joomaye Z, Ramos J, Perney P, Laurent C, Fabbro PP, Larrey D, Domergue J, Blanc F (2000) Liver iron excess in patients with hepatocellular carcinoma developed on viral C cirrhosis. Gut 46:711–714

    Article  PubMed  CAS  Google Scholar 

  49. Turlin B, Juguet F, Moirand R, Le Quilleuc D, Loreal O, Campion JP, Launois B, Ramee MP, Brissot P, Deugnier Y (1995) Increased liver iron stores in patients with hepatocellular carcinoma developed on a noncirrhotic liver. Hepatology 22:446–450

    PubMed  CAS  Google Scholar 

  50. Maeda T, Shimada M, Harimoto N, Tsujita E, Maehara S, Rikimaru T, Tanaka S, Shirabe K, Maehara Y (2005) Role of tissue trace elements in liver cancers and non-cancerous liver parenchyma. Hepatogastroenterology 52:187–190

    PubMed  CAS  Google Scholar 

  51. Ebara M, Fukuda H, Hatano R, Yoshikawa M, Sugiura N, Saisho H, Kondo F, Yukawa M (2003) Metal contents in the liver of patients with chronic liver disease caused by hepatitis C virus. Reference to hepatocellular carcinoma. Oncology 65:323–330

    Article  PubMed  CAS  Google Scholar 

  52. Honda H, Kaneko K, Kanazawa Y, Hayashi T, Fukuya T, Matsumata T, Maeda T, Masuda K (1997) MR imaging of hepatocellular carcinomas: effect of Cu and Fe contents on signal intensity. Abdom Imaging 22:60–66

    Article  PubMed  CAS  Google Scholar 

  53. Tashiro H, Kawamoto T, Okubo T, Koide O (2003) Variation in the distribution of trace elements in hepatoma. Biol Trace Elem Res 95:49–63

    Article  PubMed  CAS  Google Scholar 

  54. Iwadate H, Ohira H, Suzuki T, Abe K, Yokokawa J, Takiguchi J, Rai T, Orikasa H, Irisawa A, Obara K, Kasukawa R, Sato Y (2004) Hepatocellular carcinoma associated with Wilson’s disease. Intern Med 43:1042–1045

    Article  PubMed  Google Scholar 

  55. Kumagi T, Horiike N, Abe M, Kurose K, Iuchi H, Masumoto T, Joko K, Akbar SF, Michitaka K, Onji M (2005) Small hepatocellular carcinoma associated with Wilson’s disease. Intern Med 44:439–443

    Article  PubMed  Google Scholar 

  56. Harada M (2004) Wilson disease and hepatocellular carcinoma. Intern Med 43:1012–1013

    Article  PubMed  Google Scholar 

  57. Seth R, Yang S, Choi S, Sabean M, Roberts EA (2004) In vitro assessment of copper-induced toxicity in the human hepatoma line, Hep G2. Toxicol In Vitro 18:501–509

    Article  PubMed  CAS  Google Scholar 

  58. Sakurai H, Satoh H, Hatanaka A, Sawada T, Kawano K, Hagino T, Nakajima K (1994) Unusual generation of hydroxyl radicals in hepatic copper-metallothionein of LEC (Long–Evans cinnamon) rats in the presence of hydrogen peroxide. Biochem Biophys Res Commun 199:313–318

    Article  PubMed  CAS  Google Scholar 

  59. Suzuki KT, Rui M, Ueda J, Ozawa T (1996) Production of hydroxyl radicals by copper-containing metallothionein: roles as prooxidant. Toxicol Appl Pharmacol 141:231–237

    PubMed  CAS  Google Scholar 

  60. Hatano R, Ebara M, Fukuda H, Yoshikawa M, Sugiura N, Kondo F, Yukawa M, Saisho H (2000) Accumulation of copper in the liver and hepatic injury in chronic hepatitis C. J Gastroenterol Hepatol 15:786–791

    Article  PubMed  CAS  Google Scholar 

  61. Gupta SK, Singh SP, Shukla VK (2005) Copper, zinc, and Cu/Zn ratio in carcinoma of the gallbladder. J Surg Oncol 91:204–208

    Article  PubMed  CAS  Google Scholar 

  62. Margalioth EJ, Schenker JG, Chevion M (1983) Copper and zinc levels in normal and malignant tissues. Cancer 52:868–872

    Article  PubMed  CAS  Google Scholar 

  63. Liu XG (1991) Serum and tissue copper, zinc and selenium levels in patients with gastric carcinoma. Zhonghua Zhong Liu Za Zhi 13:93–96 [English Abstract]

    PubMed  CAS  Google Scholar 

  64. Jendryczko A, Drozdz M, Tomala J, Magner K (1986) Copper and zinc concentrations, and superoxide dismutase activities in malignant and nonmalignant tissues of female reproductive organs. Neoplasma 33:239–244

    PubMed  CAS  Google Scholar 

  65. Yoshida D, Ikeda Y, Nakazawa S (1993) Quantitative analysis of copper, zinc and copper/zinc ratio in selected human brain tumors. J Neurooncol 16:109–115

    Article  PubMed  CAS  Google Scholar 

  66. Ebara M, Fukuda H, Kojima Y, Morimoto N, Yoshikawa M, Sugiura N, Satoh T, Kondo F, Yukawa M, Matsumoto T, Saisho H (1999) Small hepatocellular carcinoma: relationship of signal intensity to histopathologic findings and metal content of the tumor and surrounding hepatic parenchyma. Radiology 210:81–88

    PubMed  CAS  Google Scholar 

  67. Haratake J, Horie A, Takeda S, Kobori K, Sato H, Tokudome S (1987) Tissue copper content in primary and metastatic liver cancers. Acta Pathol Jpn 37:231–238

    PubMed  CAS  Google Scholar 

  68. Liaw KY, Lee PH, Wu FC, Tsai JS, Lin-Shiau SY (1997) Zinc, copper, and superoxide dismutase in hepatocellular carcinoma. Am J Gastroenterol 92:2260–2263

    PubMed  CAS  Google Scholar 

  69. Goel A, Dani V, Dhawan DK (2005) Protective effects of zinc on lipid peroxidation, antioxidant enzymes hepatic histoarchitecture in chlorpyrifos-induced toxicity. Chem Biol Interact 156:131–140

    Article  PubMed  CAS  Google Scholar 

  70. Irato P, Albergoni V (2005) Interaction between copper and zinc in metal accumulation in rats with particular reference to the synthesis of induced-metallothionein. Chem Biol Interact 155:155–164

    Article  PubMed  CAS  Google Scholar 

  71. Sidhu P, Garg ML, Dhawan DK (2005) Protective effects of zinc on oxidative stress enzymes in liver of protein-deficient rats. Drug Chem Toxicol 28:211–230

    Article  PubMed  CAS  Google Scholar 

  72. Sidhu P, Garg ML, Dhawan DK (2004) Protective role of zinc in nickel induced hepatotoxicity in rats. Chem Biol Interact 150:199–209

    Article  PubMed  CAS  Google Scholar 

  73. Sreedhar B, Subramaniyan R, Nair KM (2004) A protective role for zinc on intestinal peroxidative damage during iron repletion. Biochem Biophys Res Commun 318:992–997

    Article  PubMed  CAS  Google Scholar 

  74. Gur G, Bayraktar Y, Ozer D, Ozdogan M, Kayhan B (1998) Determination of hepatic zinc content in chronic liver disease due to hepatitis B virus. Hepatogastroenterology 45:472–476

    PubMed  CAS  Google Scholar 

  75. Bode JC, Hanisch P, Henning H, Koenig W, Richter FW, Bode C (1988) Hepatic zinc content in patients with various stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis. Hepatology 8:1605–1609

    Article  PubMed  CAS  Google Scholar 

  76. Keeling PW, Ruse W, Bull J, Hannigan B, Thompson RP (1981) Direct measurement of the hepatointestinal extraction of zinc in cirrhosis and hepatitis. Clin Sci (Lond) 61:441–444

    CAS  Google Scholar 

  77. Wang H, Wei W, Zhang SY, Shen YX, Yue L, Wang NP, Xu SY (2005) Melatonin-selenium nanoparticles inhibit oxidative stress and protect against hepatic injury induced by Bacillus Calmette-Guerin/lipopolysaccharide in mice. J Pineal Res 39:156–163

    Article  PubMed  CAS  Google Scholar 

  78. Wu Q, Huang K (2004) Effect of long-term Se deficiency on the antioxidant capacities of rat vascular tissue. Biol Trace Elem Res 98:73–84

    Article  PubMed  CAS  Google Scholar 

  79. Thirunavukkarasu C, Sakthisekaran D (2003) Sodium selenite, dietary micronutrient, prevents the lymphocyte DNA damage induced by N-nitrosodiethylamine and phenobarbital promoted experimental hepatocarcinogenesis. J Cell Biochem 88:578–588

    Article  PubMed  CAS  Google Scholar 

  80. Liu S, Shia D, Liu G, Chen H, Liu S, Hu Y (2000) Roles of Se and NO in apoptosis of hepatoma cells. Life Sciences 68:603–610

    Article  PubMed  CAS  Google Scholar 

  81. Okuno T, Shimamura Y, Mizuno M, Miyata S, Miyake T, Itokawa Y, Takada J, Matsushita R, Koyama M (1988) Trace elements in hepatoma tissue. Trace Elem Med 5:130–136

    Google Scholar 

  82. GraphPad Instat [program]. 3.06, 32 bit for Windows version: GraphPad Software, Inc, 2003

  83. EndNote [program]. 8.0.2 [Bld 1150] version: Thomson, 2004.

  84. Kew MC, Mallett RC (1974) Hepatic zinc concentrations in primary cancer of the liver. Br J Cancer 29:80–83

    PubMed  CAS  Google Scholar 

  85. Honda H, Onitsuka H, Kanazawa Y, Matsumata T, Hayashi T, Kaneko K, Fukuya T, Tateshi Y, Adachi E, Masuda K (1995) MR imaging of hepatocellular carcinoma. Correlation of metal content and signal intensity. Acta Radiol 36:163–167

    Article  PubMed  CAS  Google Scholar 

  86. Nagasue N, Kohno H, Chang YC, Nakamura T (1989) Iron, copper and zinc levels in serum and cirrhotic liver of patients with and without hepatocellular carcinoma. Oncology 46:293–296

    Article  PubMed  CAS  Google Scholar 

  87. Ebara M, Fukuda H, Hatano R, Saisho H, Nagato Y, Suzuki K, Nakajima K, Yukawa M, Kondo F, Nakayama A, Sakurai H (2000) Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma. J Hepatol 33:415–422

    Article  PubMed  CAS  Google Scholar 

  88. Pascale RM, De Miglio MR, Muroni MR, Simile MM, Daino L, Seddaiu MA, Pusceddu S, Gaspa L, Calvisi D, Manenti G, Feo F (1998) Transferrin and transferrin receptor gene expression and iron uptake in hepatocellular carcinoma in the rat. Hepatology 27:452–461

    Article  PubMed  CAS  Google Scholar 

  89. Sciot R, Paterson AC, van Eyken P, Callea F, Kew MC, Desmet VJ (1988) Transferrin receptor expression in human hepatocellular carcinoma: an immunohistochemical study of 34 cases. Histopathology 12:53–63

    Article  PubMed  CAS  Google Scholar 

  90. Dameron CT, Harrison MD (1998) Mechanisms for protection against copper toxicity. Am J Clin Nutr 67:1091S–1097

    PubMed  CAS  Google Scholar 

  91. Kubo S, Fukuda H, Ebara M, Ikota N, Saisho H, Nakagawa H, Ozawa T, Yukawa M, Kato K, Satoh T, Watayo T, Sakurai H (2005) Evaluation of distribution patterns for copper and zinc in metallothionein and superoxide dismutase in chronic liver diseases and hepatocellular carcinoma using high-performance liquid chromatography (HPLC). Biol Pharm Bull 28:1137–1141

    Article  PubMed  CAS  Google Scholar 

  92. Choudhury S, Zhang R, Frenkel K, Kawamori T, Chung FL, Roy R (2003) Evidence of alterations in base excision repair of oxidative DNA damage during spontaneous hepatocarcinogenesis in Long Evans Cinnamon rats. Cancer Res 63:7704–7707

    PubMed  CAS  Google Scholar 

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  1. HBP and Liver Transplant Surgery, University Department of Surgery, Royal Free and University College School of Medicine, London, UK

    Kurinchi Gurusamy

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Gurusamy, K. Trace Element Concentration in Primary Liver Cancers—A Systematic Review. Biol Trace Elem Res 118, 191–206 (2007). https://doi.org/10.1007/s12011-007-0008-x

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