Cancer Letters
Volume 286, Issue 1 , Pages 22-28 , 1 December 2009

A model of interaction: Aflatoxins and hepatitis viruses in liver cancer aetiology and prevention

  • Christopher P. Wild

      Affiliations

    • Molecular Epidemiology Unit, Centre for Epidemiology and Biostatistics, Light Laboratories, University of Leeds, Leeds, UK
    • Corresponding Author InformationCorresponding author. Fax: +44 (0)113 343 6603.
    • ,
  • Ruggero Montesano

      Affiliations

    • 24 Via dei giardini, 11013 Courmayeur, Italy

Received 18 July 2008 ,Accepted 27 February 2009.

References 

  1. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int. J. Cancer. 2006;118:3030–3044
  2. McGlynn KA, London WT. Epidemiology and natural history of hepatocellular carcinoma. Best Pract. Res. Clin. Gastroenterol. 2005;19:3–23
  3. IARC . Alcohol Drinking. Lyon: IARC Press; 1988;
  4. IARC . Tobacco Smoke and Involuntary Smoking. Lyon: IARC Press; 2004;
  5. Jee SH, Ohrr H, Sull JW, Samet JM. Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea. J. National Cancer Instit. 2004;96:1851–1856
  6. Beasley RP, Lin CC, Hwang LY, Chien CS. Hepatocellular carcinoma and hepatitis B virus – a prospective study of 22707 men in Taiwan. Lancet. 1981;2:1129–1133
  7. IARC . Hepatitis Viruses. Lyon: IARC Press; 1994;
  8. Goldstein ST, Zhou FJ, Hadler SC, Bell BP, Mast EE, Margolis HS. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int. J. Epidemiol. 2005;34:1329–1339
  9. Tanaka Y, Kurbanov F, Mano S, Orito E, Vargas V, Esteban JI, et al. Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality. Gastroenterology. 2006;130:703–714
  10. Kurbanov F, Tanaka Y, Elkady A, Oyunsuren T, Mizokami M. Tracing hepatitis C and Delta viruses to estimate their contribution in HCC rates in Mongolia. J. Viral Hepat. 2007;14:667–674
  11. Raza SA, Clifford GM, Franceschi S. Worldwide variation in the relative importance of hepatitis B and hepatitis C viruses in hepatocellular carcinoma: a systematic review. Br. J. Cancer. 2007;96:1127–1134
  12. IARC . Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. Lyon: IARC Press; 2002;
  13. Wild CP, Turner PC. The toxicology of aflatoxins as a basis for public health decisions. Mutagenesis. 2002;17:471–481
  14. IARC . Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs. vols. 1–42. Lyon: IARC Press; 1987;
  15. IARC . Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins. Lyon: IARC Press; 1993;
  16. Hussain SP, Schwank J, Staib F, Wang XW, Harris CC. TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene. 2007;26:2166–2176
  17. Qian GS, Ross RK, Yu MC, Yuan JM, Gao YT, Henderson BE, et al. Peoples Republic of China. Cancer Epidemiol. Biomarkers Prev. 1994;3:3–10
  18. Wang LY, Hatch M, Chen CJ, Levin B, You SL, Lu SN, et al. Aflatoxin exposure and risk of hepatocellular carcinoma in Taiwan. Int. J. Cancer. 1996;67:620–625
  19. Ross RK, Yuan JM, Yu MC, Wogan GN, Qian GS, Tu JT, et al. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet. 1992;339:943–946
  20. Sun CA, Wang LY, Chen CJ, Lu SN, You SL, Wang LW, et al. Genetic polymorphisms of glutathione S-transferases M1 and TI associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: a nested case-control study in Taiwan. Carcinogenesis. 2001;22:1289–1294
  21. Yu MW, Lien JP, Chiu YH, Santella RM, Liaw YF, Chen CJ. Effect of aflatoxin metabolism and DNA adduct formation on hepatocellular carcinoma among chronic hepatitis B carriers in Taiwan. J. Hepatol. 1997;27:320–330
  22. Sun ZT, Lu PX, Gail MH, Pee D, Zhang QN, Ming LH, et al. Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1. Hepatology. 1999;30:379–383
  23. Chen CJ, Wang LY, Lu SN, Wu MH, You SL, Zhang YJ, et al. Elevated aflatoxin exposure and increased risk of hepatocellular carcinoma. Hepatology. 1996;24:38–42
  24. Kirk GD, Lesi OA, Mendy M, Akano AO, Sam O, Goedert JJ, et al. The Gambia liver cancer study: infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa. Hepatology. 2004;39:211–219
  25. Kirk GD, Lesi OA, Mendy M, Szymanska K, Whittle H, Goedert JJ, et al. TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene. 2005;24:5858–5867
  26. Kirk GD, Bah E, Montesano R. Molecular epidemiology of human liver cancer: insights into etiology, pathogenesis and prevention from The Gambia, West Africa. Carcinogenesis. 2006;27:2070–2082
  27. Omer RE, Kuijsten A, Kadaru AMY, Kok FJ, Idris MO, El Khidir IM, et al. Population-attributable risk of dietary aflatoxins and hepatitis B virus infection with respect to hepatocellular carcinoma. Nutr. Cancer. 2004;48:15–21
  28. Sun CA, Wu DM, Wang LY, Chen CJ, You SL, Santella RM. Determinants of formation of aflatoxin–albumin adducts: a seven-township study in Taiwan. Br. J. Cancer. 2002;87:966–970
  29. Chen CH, Wang MH, Wang JH, Hung CH, Hu TH, Lee SC, et al. Aflatoxin exposure and hepatitis C virus in advanced liver disease in a hepatitis C virus-endemic area in Taiwan. Am. J. Trop. Med. Hyg. 2007;77:747–752
  30. Wild CP, Kleihues P. Etiology of cancer in humans and animals. Exp. Toxicol. Pathol. 1996;48:95–100
  31. Fujimoto Y, Hampton LL, Luo LD, Wirth PJ, Thorgeirsson SS. Low-frequency of P53 gene mutation in tumors induced by aflatoxin-B1 in nonhuman primates. Cancer Res. 1992;52:1044–1046
  32. Wild CP, Jansen LAM, Cova L, Montesano R. Molecular dosimetry of aflatoxin exposure – contribution to understanding the multifactorial etiopathogenesis of primary hepatocellular carcinoma with particular reference to hepatitis B virus. Environ. Health Perspect. 1993;99:115–122
  33. Duflot A, Mehrotra R, Yu SZ, Barraud L, Trepo C, Cova L. Spectrum of liver disease and duck hepatitis B virus infection in a large series of Chinese ducks with hepatocellular carcinoma. Hepatology. 1995;21:1483–1491
  34. Cova L, Wild CP, Mehrotra R, Turusov V, Shirai T, Lambert V, et al. Contribution of aflatoxin-B1 and hepatitis B virus infection in the induction of liver tumors in ducks. Cancer Res. 1990;50:2156–2163
  35. Duflot A, Hollstein M, Mehrotra R, Trepo C, Montesano R, Cova L. Absence of P53 mutation at codon-249 in duck hepatocellular carcinomas from the high-incidence area of Qidong (China). Carcinogenesis. 1994;15:1353–1357
  36. Gouillat C, Manganas D, Zoulim F, Vitrey D, Saguier G, Guillaud M, et al. Woodchuck hepatitis virus-induced carcinoma as a relevant natural model for therapy of human hepatoma. J. Hepatol. 1997;26:1324–1330
  37. Bannasch P, Khoshkhou NI, Hacker HJ, Radaeva S, Mrozek M, Zillmann U, et al. Synergistic hepatocarcinogenic effect of hepadnaviral infection and dietary aflatoxin B-1 in woodchucks. Cancer Res. 1995;55:3318–3330
  38. Li Y, Su J, Qin L, Yang C, Ban K, Yan R. Synergistic effect of hepatitis B virus and aflatoxin B1 in hepatocarcinogenesis in tree shrews. Ann. Acad. Med. Singapore. 1999;28:67–71
  39. Sell S. Mouse models to study the interaction of risk factors for human liver cancer. Cancer Res. 2003;63:7553–7562
  40. Ghebranious N, Sell S. The mouse equivalent of the human p53ser249 mutation p53ser246 enhances aflatoxin hepatocarcinogenesis in hepatitis B surface antigen transgenic and p53 heterozygous null mice. Hepatology. 1998;27:967–973
  41. Sell S, Hunt JM, Dunsford HA, Chisari FV. Synergy between hepatitis-B virus expression and chemical hepatocarcinogens in transgenic mice. Cancer Res. 1991;51:1278–1285
  42. Lian M, Liu Y, Yu SZ, Qian GS, Wan SG, Dixon KR. Hepatitis B virus x gene and cyanobacterial toxins promote aflatoxin B-1-induced hepatotumorigenesis in mice. World J. Gastroenterol. 2006;12:3065–3072
  43. Tong WM, Lee MK, Galendo D, Wang ZQ, Sabapathy K. Aflatoxin-B exposure does not lead to p53 mutations but results in enhanced liver cancer of Hupki (human p53 knock-in) mice. Int. J. Cancer. 2006;119:745–749
  44. Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang UY, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. New Engl. J. Med. 2002;347:168–174
  45. Lee JS, Thorgeirsson SS. Comparative and integrative functional genomics of HCC. Oncogene. 2006;25:3801–3809
  46. Kremsdorf D, Soussan P, Paterlini-Brechot P, Brechot C. Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis. Oncogene. 2006;25:3823–3833
  47. Minami M, Daimon Y, Mori K, Takashima H, Nakajima T, Itoh Y, et al. Hepatitis B virus-related insertional mutagenesis in chronic hepatitis B patients as an early drastic genetic change leading to hepatocarcinogenesis. Oncogene. 2005;24:4340–4348
  48. Dunsford HA, Sell S, Chisari FV. Hepatocarcinogenesis due to chronic liver-cell injury in hepatitis-B virus transgenic mice. Cancer Res. 1990;50:3400–3407
  49. Wu HC, Wang Q, Wang LW, Yang HI, Ahsan H, Tsai WY, et al. Urinary 8-oxodeoxyguanosine, aflatoxin B-1 exposure and hepatitis B virus infection and hepatocellular carcinoma in Taiwan. Carcinogenesis. 2007;28:995–999
  50. Liu ZM, Li LQ, Peng MH, Liu TW, Qin Z, Guo Y, et al. Hepatitis B virus infection contributes to oxidative stress in a population exposed to aflatoxin B1 and high-risk for hepatocellular carcinoma. Cancer Lett. 2008;263:212–222
  51. Wong RH, Yeh CY, Hsueh YM, Wang JD, Lei YC, Cheng TJ. Association of hepatitis virus infection, alcohol consumption and plasma vitamin A levels with urinary 8-hydroxydeoxyguanosine in chemical workers. Mut. Res. Gen. Toxicol. Environ. 2003;535:181–186
  52. Fujita N, Sugimoto R, Ma N, Tanaka H, Iwasa M, Kobayashi Y, et al. Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C. J. Viral Hepat. 2008;15:498–507
  53. Sohn S, Jaitovitch-Groisman I, Benlimame N, Galipeau J, Batist G, Alaoui-Jamali MA. Retroviral expression of the hepatitis B virus x gene promotes liver cell susceptibility to carcinogen-induced site specific mutagenesis. Mutat. Res. DNA Repair. 2000;460:17–28
  54. Kew MC. Synergistic interaction between aflatoxin B-1 and hepatitis B virus in hepatocarcinogenesis. Liver Int. 2003;23:405–409
  55. Deflora S, Hietanen E, Bartsch H, Camoirano A, Izzotti A, Bagnasco M, et al. Enhanced metabolic-activation of chemical hepatocarcinogens in woodchucks infected with hepatitis-B virus. Carcinogenesis. 1989;10:1099–1106
  56. Gemechu-Hatewu M, Platt KL, Oesch F, Hacker HJ, Bannasch P, Steinberg P. Metabolic activation of aflatoxin B-1 to aflatoxin B-1-8-9-epoxide in woodchucks undergoing chronic active hepatitis. Int. J. Cancer. 1997;73:587–591
  57. Chemin I, Takahashi S, Belloc C, Lang MA, Ando K, Guidotti LG, et al. Differential induction of carcinogen metabolizing enzymes in a transgenic mouse model of fulminant hepatitis. Hepatology. 1996;24:649–656
  58. Kirby GM, Chemin I, Montesano R, Chisari FV, Lang MA, Wild CP. Induction of specific cytochrome P450s involved in aflatoxin B-1 metabolism in hepatitis-B virus transgenic mice. Mol. Carcinog. 1994;11:74–80
  59. Chomarat P, Rice JM, Slagle BL, Wild CP. Hepatitis B virus-induced liver injury and altered expression of carcinogen metabolising enzymes: the role of the HBx protein. Toxicol. Lett. 1998;103:595–601
  60. Chemin I, Ohgaki H, Chisari FV, Wild CP. Altered expression of hepatic carcinogen metabolizing enzymes with liver injury in HBV transgenic mouse lineages expressing various amounts of hepatitis B surface antigen. Liver. 1999;19:81–87
  61. Jaitovitch-Groisman I, Fotouhi-Ardakani N, Schecter RL, Woo A, Alaoui-Jamali MA, Batist G. Modulation of glutathione S-transferase alpha by hepatitis B virus and the chemopreventive drug oltipraz. J. Biol. Chem. 2000;275:33395–33403
  62. Zhou TL, Evans AA, London WT, Xia XL, Zou HQ, Shen FM, et al. Glutathione S-transferase expression in hepatitis B virus-associated human hepatocellular carcinogenesis. Cancer Res. 1997;57:2749–2753
  63. Barraud L, Guerret S, Chevallier M, Borel C, Jamard C, Trepo C, et al. Enhanced duck hepatitis B virus gene expression following aflatoxin B-1 exposure. Hepatology. 1999;29:1317–1323
  64. Banerjee R, Caruccio L, Zhang YJ, McKercher S, Santella RM. Effects of carcinogen-induced transcription factors on the activation of hepatitis B virus expression in human hepatoblastoma HepG2 cells and its implication on hepatocellular carcinomas. Hepatology. 2000;32:367–374
  65. Dandri M, Burda MR, Burkle A, Zuckerman DM, Will H, Rogler CE, et al. Increase in de novo HBV DNA integrations in response to oxidative DNA damage or inhibition of poly(ADP-ribosyl)ation. Hepatology. 2002;35:217–223
  66. Turner PC, Moore SE, Hall AJ, Prentice AM, Wild CP. Modification of immune function through exposure to dietary aflatoxin in Gambian children. Environ. Health Perspect. 2003;111:217–220
  67. Global and Regional Immunization Profile. <http://www.who.int/immunization_monitoring/en/globalsummary/GS_AFRProfile.pdf>.
  68. Hall AJ, Wild CP. Liver cancer in low and middle income countries – prevention should target vaccination, contaminated needles, and aflatoxins. Br. Med. J. 2003;326:994–995
  69. Wild CP, Hall AJ. Primary prevention of hepatocellular carcinoma in developing countries. Mutat. Res. Rev. Mutat. 2000;462:381–393
  70. Groopman JD, Kensler TW, Wild CP. Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countries. Annu. Rev. Public Health. 2008;29:187–203
  71. Gong YY, Cardwell K, Hounsa A, Egal S, Turner PC, Hall AJ, et al. Dietary aflatoxin exposure and impaired growth in young children from Benin and Togo: cross sectional study. Br. Med. J. 2002;325:20–21
  72. Gong YY, Hounsa A, Egal S, Turner PC, Sutcliffe AE, Hall AJ, et al. Postweaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, west Africa. Environ. Health Perspect. 2004;112:1334–1338
  73. ChinaFood, Can China Feed Itself? <http://www.iiasa.ac.at/docs/Research/LUC/ChinaFood/indepth/id_4.htm>.
  74. Turner PC, Sylla A, Gong YY, Diailo MS, Sutcliffe AE, Hall AJ, et al. Reduction in exposure to carcinogenic aflatoxins by postharvest intervention measures in west Africa: a community-based intervention study. Lancet. 2005;365:1950–1956
  75. Wang P, Afriyie-Gyawu E, Tang Y, Johnson NM, Xu L, Tang L, et al. NovaSil clay intervention in Ghanaians at high risk for aflatoxicosis: II. Reduction in biomarkers of aflatoxin exposure in blood and urine. Food Addit. Contam. 2008;25:622–634
  76. Egner PA, Wang JB, Zhu YR, Zhang BC, Wu Y, Zhang QN, et al. Chlorophyllin intervention reduces aflatoxin–DNA adducts in individuals at high risk for liver cancer. Proc. Natl. Acad. Sci. USA. 2001;98:14601–14606
  77. Tang LL, Tang M, Xu L, Luo HT, Huang TR, Yu JH, et al. Modulation of aflatoxin biomarkers in human blood and urine by green tea polyphenols intervention. Carcinogenesis. 2008;29:411–417
  78. Kensler TW, Chen JG, Egner PA, Fahey JW, Jacobson LP, Stephenson KK, et al. Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin–DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People’s Republic of China. Cancer Epidemiol. Biomarkers Prev. 2005;14:2605–2613
  79. Azziz-Baumgartner E, Lindblade K, Gieseker K, Rogers HS, Kieszak S, Njapau H, et al. Case-control study of an acute aflatoxicosis outbreak, Kenya, 2004. Environ. Health Perspect. 2005;113:1779–1783
  80. Wild CP. Aflatoxin exposure in developing countries: the critical interface of agriculture and health. Food Nutr. Bull. 2007;28:S372–S380
  81. Hulla JE, Chen ZY, Eaton DL. Aflatoxin-B1-induced rat hepatic hyperplastic nodules do not exhibit a site-specific mutation within the P53 gene. Cancer Res. 1993;53:9–11
  82. Lee CC, Liu JY, Lin JK, Chu JS, Shew JY. p53 point mutation enhanced by hepatic regeneration in aflatoxin B-1-induced rat liver tumors and preneoplastic lesions. Cancer Lett. 1998;125:1–7
  83. Rivkina M, Cote PJ, Robinson WS, Tennant BC, Marion PL. Absence of mutations in the p53 tumor suppressor gene in woodchuck hepatocellular carcinomas associated with hepadnavirus infection and intake of aflatoxin B-1. Carcinogenesis. 1996;17:2689–2694
  84. Rivkina MB, Cullen JM, Robinson WS, Marion PL. State of the P53 gene in hepatocellular carcinomas of ground-squirrels and woodchucks with past and ongoing infection with hepadnaviruses. Cancer Res. 1994;54:5430–5437
  85. Park US, Su JJ, Ban KC, Qin LL, Lee EH, Lee YI. Mutations in the p53 tumor suppressor gene in tree shrew hepatocellular carcinoma associated with hepatitis B virus infection and intake of aflatoxin B1. Gene. 2000;251:73–80
  86. Luo JL, Yang Q, Tong WM, Hergenhahn M, Wang ZQ, Hollstein M. Knock-in mice with a chimeric human/murine p53 gene develop normally and show wild-type p53 responses to DNA damaging agents: a new biomedical research tool. Oncogene. 2001;20:320–328

PII: S0304-3835(09)00168-2

doi: 10.1016/j.canlet.2009.02.053

Cancer Letters
Volume 286, Issue 1 , Pages 22-28 , 1 December 2009

Article Tools