Skip to main content
PMC home page
Gut logoLink to Gut
. 1995 Nov;37(5):727–730. doi: 10.1136/gut.37.5.727

Hepatocellular carcinoma and African iron overload.

I T Gangaidzo 1, V R Gordeuk 1
PMCID: PMC1382882  PMID: 8549953

Abstract

Both hepatocellular carcinoma (HCC) and iron overload are important health problems in Africa. Chronic hepatitis B virus (HBV) infection is recognised as a major risk factor for HCC, but iron overload in Africans has not been considered in pathogenesis. Up to half the patients with HCC in Africa do not have any recognised risk factors such as preceding chronic HBV infection, and other risk factors remain unidentified. HCC is an important complication of HLA-linked haemochromatosis, an iron loading disorder found in Europeans. It is proposed that African iron overload might also be a risk factor for HCC.

Full text

PDF
730

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BOTHWELL T. H., ABRAHAMS C., BRADLOW B. A., CHARLTON R. W. IDIOPATHIC AND BANTU HEMOCHROMATOSIS. COMPARATIVE HISTOLOGICAL STUDY. Arch Pathol. 1965 Feb;79:163–168. [PubMed] [Google Scholar]
  2. BOTHWELL T. H., BRADLOW B. A. Siderosis in the Bantu. A combined histopathological and chemical study. Arch Pathol. 1960 Sep;70:279–292. [PubMed] [Google Scholar]
  3. BOTHWELL T. H., SEFTEL H., JACOBS P., TORRANCE J. D., BAUMSLAG N. IRON OVERLOAD IN BANTU SUBJECTS; STUDIES ON THE AVAILABILITY OF IRON IN BANTU BEER. Am J Clin Nutr. 1964 Jan;14:47–51. doi: 10.1093/ajcn/14.1.47. [DOI] [PubMed] [Google Scholar]
  4. BUTT E. M., HIGGINSON J. Trace element pattern in liver disease and liver carcinoma. Acta Unio Int Contra Cancrum. 1957;13(4-5):599–601. [PubMed] [Google Scholar]
  5. Barin F., Perrin J., Chotard J., Denis F., N'Doye R., Diop Mar I., Chiron J. P., Coursaget P., Goudeau A., Maupas P. Cross-sectional and longitudinal epidemiology of hepatitis B in Senegal. Prog Med Virol. 1981;27:148–162. [PubMed] [Google Scholar]
  6. Beasley R. P., Hwang L. Y., Lin C. C., Chien C. S. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 1981 Nov 21;2(8256):1129–1133. doi: 10.1016/s0140-6736(81)90585-7. [DOI] [PubMed] [Google Scholar]
  7. Blumberg R. S., Chopra S., Ibrahim R., Crawford J., Farraye F. A., Zeldis J. B., Berman M. D. Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis. Gastroenterology. 1988 Nov;95(5):1399–1402. doi: 10.1016/0016-5085(88)90379-4. [DOI] [PubMed] [Google Scholar]
  8. Brink B., Disler P., Lynch S., Jacobs P., Charlton R., Bothwell T. Patterns of iron storage in dietary iron overload and idiopathic hemochromatosis. J Lab Clin Med. 1976 Nov;88(5):725–731. [PubMed] [Google Scholar]
  9. DODU S. R. Diabetes and haemosiderosis, haemochromatosis, in Ghana. Trans R Soc Trop Med Hyg. 1958 Sep;52(5):425–430. doi: 10.1016/0035-9203(58)90128-7. [DOI] [PubMed] [Google Scholar]
  10. Dusheiko G. Hepatocellular carcinoma: molecular biology, etiology and animal models. Gastroenterol Clin North Am. 1987 Dec;16(4):575–590. [PubMed] [Google Scholar]
  11. Edwards C. Q., Griffen L. M., Goldgar D., Drummond C., Skolnick M. H., Kushner J. P. Prevalence of hemochromatosis among 11,065 presumably healthy blood donors. N Engl J Med. 1988 May 26;318(21):1355–1362. doi: 10.1056/NEJM198805263182103. [DOI] [PubMed] [Google Scholar]
  12. Fellows I. W., Stewart M., Jeffcoate W. J., Smith P. G., Toghill P. J. Hepatocellular carcinoma in primary haemochromatosis in the absence of cirrhosis. Gut. 1988 Nov;29(11):1603–1606. doi: 10.1136/gut.29.11.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Friedman B. M., Baynes R. D., Bothwell T. H., Gordeuk V. R., Macfarlane B. J., Lamparelli R. D., Robinson E. J., Sher R., Hamberg S. Dietary iron overload in southern African rural blacks. S Afr Med J. 1990 Sep 15;78(6):301–305. [PubMed] [Google Scholar]
  14. Gordeuk V. R., Boyd R. D., Brittenham G. M. Dietary iron overload persists in rural sub-Saharan Africa. Lancet. 1986 Jun 7;1(8493):1310–1313. doi: 10.1016/s0140-6736(86)91230-4. [DOI] [PubMed] [Google Scholar]
  15. Gordeuk V. R. Hereditary and nutritional iron overload. Baillieres Clin Haematol. 1992 Jan;5(1):169–186. doi: 10.1016/s0950-3536(11)80040-5. [DOI] [PubMed] [Google Scholar]
  16. Gordeuk V. R., McLaren G. D., Samowitz W. Etiologies, consequences, and treatment of iron overload. Crit Rev Clin Lab Sci. 1994;31(2):89–133. doi: 10.3109/10408369409084674. [DOI] [PubMed] [Google Scholar]
  17. Gordeuk V., Mukiibi J., Hasstedt S. J., Samowitz W., Edwards C. Q., West G., Ndambire S., Emmanual J., Nkanza N., Chapanduka Z. Iron overload in Africa. Interaction between a gene and dietary iron content. N Engl J Med. 1992 Jan 9;326(2):95–100. doi: 10.1056/NEJM199201093260204. [DOI] [PubMed] [Google Scholar]
  18. Gutteridge J. M., Rowley D. A., Griffiths E., Halliwell B. Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. Clin Sci (Lond) 1985 Apr;68(4):463–467. doi: 10.1042/cs0680463. [DOI] [PubMed] [Google Scholar]
  19. HADDOCK D. R. BANTU SIDEROSIS IN TANZANIA. East Afr Med J. 1965 Feb;42:67–73. [PubMed] [Google Scholar]
  20. HIGGINSON J., DE MEILLON B. Schistosoma haematobium infestation and hepatic disease in man. AMA Arch Pathol. 1955 Sep;60(3):341–346. [PubMed] [Google Scholar]
  21. HIGGINSON J., GERRITSEN T., WALKER A. R. Siderosis in the Bantu of Southern Africa. Am J Pathol. 1953 Jul-Aug;29(4):779–815. [PMC free article] [PubMed] [Google Scholar]
  22. HIGGINSON J. Pathogenesis of liver cancer in the Johannesburg area (S. Africa). Acta Unio Int Contra Cancrum. 1957;13(4-5):590–598. [PubMed] [Google Scholar]
  23. HIGGINSON J. Primary carcinoma of the liver in Africa. Br J Cancer. 1956 Dec;10(4):609–622. doi: 10.1038/bjc.1956.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. HIGGINSON J. THE GEOGRAPHICAL PATHOLOGY OF PRIMARY LIVER CANCER. Cancer Res. 1963 Nov;23:1624–1633. [PubMed] [Google Scholar]
  25. Halliwell B., Gutteridge J. M., Cross C. E. Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med. 1992 Jun;119(6):598–620. [PubMed] [Google Scholar]
  26. Hann H. W., Stahlhut M. W., Hann C. L. Effect of iron and desferoxamine on cell growth and in vitro ferritin synthesis in human hepatoma cell lines. Hepatology. 1990 Apr;11(4):566–569. doi: 10.1002/hep.1840110407. [DOI] [PubMed] [Google Scholar]
  27. Hershko C., Graham G., Bates G. W., Rachmilewitz E. A. Non-specific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity. Br J Haematol. 1978 Oct;40(2):255–263. doi: 10.1111/j.1365-2141.1978.tb03662.x. [DOI] [PubMed] [Google Scholar]
  28. Hershko C. Storage iron regulation. Prog Hematol. 1977;10:105–148. [PubMed] [Google Scholar]
  29. Isah H. S., Fleming A. F. Anaemia and iron status of symptom-free adult males in northern Nigeria. Ann Trop Med Parasitol. 1985 Oct;79(5):479–484. doi: 10.1080/00034983.1985.11811951. [DOI] [PubMed] [Google Scholar]
  30. Jaskiewicz K., Stepien A., Banach L. Hepatocellular carcinoma in a rural population at risk. Anticancer Res. 1991 Nov-Dec;11(6):2187–2189. [PubMed] [Google Scholar]
  31. Kew M. C., Desmyter J., Bradburne A. F., Macnab G. M. Hepatitis B virus infection in southern African blacks with hepatocellular cancer. J Natl Cancer Inst. 1979 Mar;62(3):517–520. doi: 10.1093/jnci/62.3.517. [DOI] [PubMed] [Google Scholar]
  32. Kew M. C. Hepatocellular carcinoma with and without cirrhosis. A comparison in southern African blacks. Gastroenterology. 1989 Jul;97(1):136–139. doi: 10.1016/0016-5085(89)91426-1. [DOI] [PubMed] [Google Scholar]
  33. Kew M. C., Rossouw E., Hodkinson J., Paterson A., Dusheiko G. M., Whitcutt J. M. Hepatitis B virus status of southern African Blacks with hepatocellular carcinoma: comparison between rural and urban patients. Hepatology. 1983 Jan-Feb;3(1):65–68. doi: 10.1002/hep.1840030110. [DOI] [PubMed] [Google Scholar]
  34. LEEVY C. M., GELLENE R., NING M. PRIMARY LIVER CANCER IN CIRRHOSIS OF THE ALCOHOLIC. Ann N Y Acad Sci. 1964 Apr 2;114:1026–1040. [PubMed] [Google Scholar]
  35. Larouzé B., Blumberg B. S., London W. T., Lustbader E. D., Sankalé M., Payet M. Forecasting the development of primary hepatocellular carcinoma by the use of risk factors: studies in West Africa. J Natl Cancer Inst. 1977 Jun;58(6):1557–1561. doi: 10.1093/jnci/58.6.1557. [DOI] [PubMed] [Google Scholar]
  36. Loeb L. A., James E. A., Waltersdorph A. M., Klebanoff S. J. Mutagenesis by the autoxidation of iron with isolated DNA. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3918–3922. doi: 10.1073/pnas.85.11.3918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Lutwick L. I. Relation between aflatoxin, hepatitis-B virus, and hepatocellular carcinoma. Lancet. 1979 Apr 7;1(8119):755–757. doi: 10.1016/s0140-6736(79)91210-8. [DOI] [PubMed] [Google Scholar]
  38. Mohamed A. E., Kew M. C., Groeneveld H. T. Alcohol consumption as a risk factor for hepatocellular carcinoma in urban southern African blacks. Int J Cancer. 1992 Jun 19;51(4):537–541. doi: 10.1002/ijc.2910510406. [DOI] [PubMed] [Google Scholar]
  39. Niederau C., Fischer R., Sonnenberg A., Stremmel W., Trampisch H. J., Strohmeyer G. Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N Engl J Med. 1985 Nov 14;313(20):1256–1262. doi: 10.1056/NEJM198511143132004. [DOI] [PubMed] [Google Scholar]
  40. Owor R. Haemosiderosis in Uganda: autopsy study. East Afr Med J. 1974 May;51(5):388–391. [PubMed] [Google Scholar]
  41. Paterson A. C., Kew M. C., Herman A. A., Becker P. J., Hodkinson J., Isaacson C. Liver morphology in southern African blacks with hepatocellular carcinoma: a study within the urban environment. Hepatology. 1985 Jan-Feb;5(1):72–78. doi: 10.1002/hep.1840050116. [DOI] [PubMed] [Google Scholar]
  42. Peers F., Bosch X., Kaldor J., Linsell A., Pluijmen M. Aflatoxin exposure, hepatitis B virus infection and liver cancer in Swaziland. Int J Cancer. 1987 May 15;39(5):545–553. doi: 10.1002/ijc.2910390502. [DOI] [PubMed] [Google Scholar]
  43. Ryder R. W., Whittle H. C., Sanneh A. B., Ajdukiewicz A. B., Tulloch S., Yvonnet B. Persistent hepatitis B virus infection and hepatoma in The Gambia, west Africa. A case-control study of 140 adults and their 603 family contacts. Am J Epidemiol. 1992 Nov 1;136(9):1122–1131. doi: 10.1093/oxfordjournals.aje.a116578. [DOI] [PubMed] [Google Scholar]
  44. Whittaker P., Skikne B. S., Covell A. M., Flowers C., Cooke A., Lynch S. R., Cook J. D. Duodenal iron proteins in idiopathic hemochromatosis. J Clin Invest. 1989 Jan;83(1):261–267. doi: 10.1172/JCI113868. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES