Skip to main content

Aflatoxin and Hepatocellular Carcinoma

  • Chapter
  • First Online:
Chemical Carcinogenesis

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer morbidity and mortality in many parts of the world, including Asia and sub-Saharan Africa, where there are upwards of 600,000 new cases each year. Over 80% of the burden of HCC is manifest in the economically developing world. Further, the median age of diagnosis and death from HCC is between 45 and 55 years of age in these regions. Since the occurrence of HCC is coincident with regions where aflatoxin exposure is high, efforts started in the 1960s to investigate this possible association. Aflatoxin biomarkers of internal and biologically effective dose have been integral to definitively establish the etiologic role of this toxin in human HCC. In two separate cohort studies, a strong multiplicative relationship between aflatoxin exposure and the hepatitis B virus for the development of HCC was found. Further, in recent years, research has demonstrated that aflatoxin exposure is also linked to the occurrence of a specific mutation in the p53 tumor suppressor gene. Thus, the development and application of molecular biomarkers reflecting events from exposure to manifestation of clinical disease has rapidly expanded our knowledge of the mechanisms of disease pathogenesis in HCC, and this will have increasing potential for early detection, treatment, interventions, and prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 179.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 229.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adamson RH, Correa P, Sieber SM, McIntire KR, Dalgard DW. (1976). J Natl Cancer Inst 57:67–78

    PubMed  CAS  Google Scholar 

  • Aguilar F, Hussain SP, Cerutti P. (1993). Proc Natl Acad Sci USA 90:8586–90

    Article  PubMed  CAS  Google Scholar 

  • Arbuthnot P, Kew M. (2001). Int J Exp Pathol 82:77–100

    Article  PubMed  CAS  Google Scholar 

  • Asao T, Buchi G, Abdel-Kader M, Chang S, Wick E, Wogan GN. (1963). J Am Chem Soc 85:1706–7

    Article  CAS  Google Scholar 

  • Autrup H, Bradley KA, Shamsuddin AK, Wakhisi J, Wasunna A. (1983). Carcinogenesis 4:1193–5

    Article  PubMed  CAS  Google Scholar 

  • Autrup H, Seremet T, Wakhisi J, Wasunna A. (1987). Cancer Res 47:3430–3

    PubMed  CAS  Google Scholar 

  • Bailey GS, Loveland PM, Pereira C, Pierce D, Hendricks JD, Groopman JD. (1994). Mutat Res 313:25–38

    PubMed  CAS  Google Scholar 

  • Bennett RA, Essigmann JM, Wogan GN. (1981). Cancer Res 41:650–4

    PubMed  CAS  Google Scholar 

  • Blount WP. (1961). J Br Turkey Fed 9:55–8

    Google Scholar 

  • Bolton MG, Munoz A, Jacobson LP, Groopman JD, Maxuitenko YY, et al. (1993). Cancer Res 53:3499–504

    PubMed  CAS  Google Scholar 

  • Bressac B, Kew M, Wands J, Ozturk M. (1991). Nature 350:429–31

    Article  PubMed  CAS  Google Scholar 

  • Bulatao-Jayme J, Almero EM, Castro MC, Jardeleza MT, Salamat LA. (1982). Int J Epidemiol 11:112–9

    Article  PubMed  CAS  Google Scholar 

  • Busby WF, Wogan GN. (1984a). Aflatoxins. Washington, DC: American Chemical Society. pp. 945–1136

    Google Scholar 

  • Busby WFJ, Wogan GN. (1984b). Aflatoxins. In Chemical Carcinogens, ed. CD Searle, pp. 945–1136. Washington, DC: American Chemical Society

    Google Scholar 

  • Campbell TC, Caedo JP, Jr., Bulatao-Jayme J, Salamat L, Engel RW. (1970). Nature 227:403–4

    Article  PubMed  CAS  Google Scholar 

  • Campbell AD, Whitaker TB, Pohland AE, Dickens JW, Park DL. (1986). Pure Appl Chem 58:305–14

    Article  CAS  Google Scholar 

  • Chen JG, Zhu J, Parkin DM, Zhang YH, Lu JH, et al. (2006). Int J Cancer 119:1447–54

    Article  PubMed  CAS  Google Scholar 

  • Croy RG, Wogan GN. (1981). J Natl Cancer Inst 66:761–7

    PubMed  CAS  Google Scholar 

  • Denissenko MF, Koudriakova TB, Smith L, O’Connor TR, Riggs AD, Pfeifer GP. (1998). Oncogene 17:3007–14

    Article  PubMed  CAS  Google Scholar 

  • Eaton DL, Groopman JD. (1994). The Toxicology of Aflatoxins: Human Health, Veterinary, and Agricultural Significance. San Diego, CA: Academic Press

    Google Scholar 

  • Egner PA, Gange SJ, Dolan PM, Groopman JD, Munoz A, Kensler TW. (1995). Carcinogenesis 16:1769–73

    Article  PubMed  CAS  Google Scholar 

  • Egner PA, Groopman JD, Wang JS, Kensler TW, Friesen MD. (2006). Chem Res Toxicol 19:1191–5

    Article  PubMed  CAS  Google Scholar 

  • Essigmann JM, Croy RG, Nadzan AM, Busby WF, Jr., Reinhold VN, et al. (1977). Proc Natl Acad Sci USA 74:1870–4

    Article  PubMed  CAS  Google Scholar 

  • Ferlay J, Bray F, Pisani P, Parkin DM. (2004). GLOBOCAN 2002, Cancer Incidence, Mortality and Prevalence Worldwide, IARC CancerBase No. 5, version 2.0. Lyon: IARC

    Google Scholar 

  • Foster PL, Eisenstadt E, Miller JH. (1983). Proc Natl Acad Sci USA 80:2695–8

    Article  PubMed  CAS  Google Scholar 

  • Gan LS, Skipper PL, Peng XC, Groopman JD, Chen JS, et al. (1988). Carcinogenesis 9:1323–5

    Article  PubMed  CAS  Google Scholar 

  • Gopalan C, Tulpule PG, Krishnamurthi D. (1972). Food Cosmet Toxicol 10:519–21

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt MS, Bennett WP, Hollstein M, Harris CC. (1994). Cancer Res 54:4855–78

    PubMed  CAS  Google Scholar 

  • Groopman JD, Kensler TW. (2005). Toxicol Appl Pharmacol 206:131–7

    Article  PubMed  CAS  Google Scholar 

  • Groopman JD, Trudel LJ, Donahue PR, Marshak-Rothstein A, Wogan GN. (1984). Proc Natl Acad Sci USA 81:7728–31

    Article  PubMed  CAS  Google Scholar 

  • Groopman JD, Donahue PR, Zhu JQ, Chen JS, Wogan GN. (1985). Proc Natl Acad Sci USA 82:6492–6

    Article  PubMed  CAS  Google Scholar 

  • Groopman JD, DeMatos P, Egner PA, Love-Hunt A, Kensler TW. (1992a). Carcinogenesis 13:101–6

    Article  PubMed  CAS  Google Scholar 

  • Groopman JD, Hall AJ, Whittle H, Hudson GJ, Wogan GN, et al. (1992b). Cancer Epidemiol Biomarkers Prev 1:221–7

    PubMed  CAS  Google Scholar 

  • Groopman JD, Hasler JA, Trudel LJ, Pikul A, Donahue PR, Wogan GN. (1992c). Cancer Res 52:267–74

    PubMed  CAS  Google Scholar 

  • Groopman JD, Zhu JQ, Donahue PR, Pikul A, Zhang LS, et al. (1992d). Cancer Res 52:45–52

    PubMed  CAS  Google Scholar 

  • Groopman JD, Kensler TW, Wild CP. (2008). Annu Rev Public Health 29:187–203

    Article  PubMed  Google Scholar 

  • Harris CC. (1993). Multistep carcinogenesis. Jpn J Cancer Res 84:inside front cover

    PubMed  CAS  Google Scholar 

  • Harris CC. (1994). Cancer Epidemiol Biomarkers Prev 3:1–2

    PubMed  Google Scholar 

  • Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC. (1991). Nature 350:427–8

    Article  PubMed  CAS  Google Scholar 

  • Hussain SP, Schwank J, Staib F, Wang XW, Harris CC. (2007). Oncogene 26:2166–76

    Article  PubMed  CAS  Google Scholar 

  • IARC. (1993). Aflatoxins. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans/World Health Organization, International Agency for Research on Cancer. Vol 56. Lyon: IARC. pp. 245–395

    Google Scholar 

  • Jackson PE, Qian GS, Friesen MD, Zhu YR, Lu P, et al. (2001). Cancer Res 61:33–5

    PubMed  CAS  Google Scholar 

  • Jackson PE, Kuang SY, Wang JB, Strickland PT, Munoz A, et al. (2003). Carcinogenesis 24:1657–63

    Article  PubMed  CAS  Google Scholar 

  • Kensler TW, Egner PA, Trush MA, Bueding E, Groopman JD. (1985). Carcinogenesis 6:759–63

    Article  PubMed  CAS  Google Scholar 

  • Kensler TW, Egner PA, Davidson NE, Roebuck BD, Pikul A, Groopman JD. (1986). Cancer Res 46:3924–31

    PubMed  CAS  Google Scholar 

  • Kensler TW, Gange SJ, Egner PA, Dolan PM, Munoz A, et al. (1997). Cancer Epidemiol Biomarkers Prev 6:603–10

    PubMed  CAS  Google Scholar 

  • Kew MC. (2002). Toxicology 181–182:35–8

    Article  PubMed  Google Scholar 

  • Kirk GD, Camus-Randon AM, Mendy M, Goedert JJ, Merle P, et al. (2000). J Natl Cancer Inst 92:148–53

    Article  PubMed  CAS  Google Scholar 

  • Lancaster MC, Jenkins FP, Philp JM. (1961). Nature 192:1095–6

    Article  Google Scholar 

  • Lunn RM, Zhang YJ, Wang LY, Chen CJ, Lee PH, et al. (1997). Cancer Res 57:3471–7

    PubMed  CAS  Google Scholar 

  • Lutz WK. (1987). Arch Toxicol Suppl 11:66–74

    PubMed  CAS  Google Scholar 

  • McGlynn KA, Rosvold EA, Lustbader ED, Hu Y, Clapper ML, et al. (1995). Proc Natl Acad Sci USA 92:2384–7

    Article  PubMed  CAS  Google Scholar 

  • Ming L, Thorgeirsson SS, Gail MH, Lu P, Harris CC, et al. (2002). Hepatology 36:1214–20

    Article  PubMed  CAS  Google Scholar 

  • Nesbitt BF, O’Kelly J, Sargeant K, Sheridan A. (1962). Nature 195:1062–3

    Article  PubMed  CAS  Google Scholar 

  • Parkin DM, Bray F, Ferlay J, Pisani P. (2005). CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  • Peers FG, Linsell CA. (1977). Ann Nutr Aliment 31:1005–17

    PubMed  CAS  Google Scholar 

  • Poirier MC, Santella RM, Weston A. (2000). Carcinogenesis 21:353–9

    Article  PubMed  CAS  Google Scholar 

  • Probst C, Njapau H, Cotty PJ. (2007). Appl Environ Microbiol 73:2762–4

    Article  PubMed  CAS  Google Scholar 

  • Puisieux A, Lim S, Groopman J, Ozturk M. (1991). Cancer Res 51:6185–9

    PubMed  CAS  Google Scholar 

  • Qian GS, Ross RK, Yu MC, Yuan JM, Gao YT, et al. (1994). Cancer Epidemiol Biomarkers Prev 3:3–10

    PubMed  CAS  Google Scholar 

  • Richard JL, Bennett GA, Ross PF, Nelson PE. (1993). J Anim Sci 71:2563–74

    PubMed  CAS  Google Scholar 

  • Roebuck BD, Liu YL, Rogers AE, Groopman JD, Kensler TW. (1991). Cancer Res 51:5501–6

    PubMed  CAS  Google Scholar 

  • Ross RK, Yuan JM, Yu MC, Qian GS, Tu JT, et al. (1992a). Lancet 339:943–6

    Article  PubMed  CAS  Google Scholar 

  • Ross RK, Yuan JM, Yu MC, Wogan GN, Qian GS, et al. (1992b). Lancet 339:943–6

    Article  PubMed  CAS  Google Scholar 

  • Sabbioni G, Skipper PL, Buchi G, Tannenbaum SR. (1987). Carcinogenesis 8:819–24

    Article  PubMed  CAS  Google Scholar 

  • Santella RM. (1999). Cancer Epidemiol Biomarkers Prev 8:733–9

    PubMed  CAS  Google Scholar 

  • Sargeant K, Sheridan A, O’Kelly J, Carnaghan RBA. (1961). Nature 192:1096–7

    Article  Google Scholar 

  • Scholl PF, Groopman JD. (2008). Cancer Epidemiol Biomarkers Prev 17:1436–9

    Article  PubMed  CAS  Google Scholar 

  • Scholl PF, McCoy L, Kensler TW, Groopman JD. (2006a). Chem Res Toxicol 19:44–9

    Article  PubMed  CAS  Google Scholar 

  • Scholl PF, Turner PC, Sutcliffe AE, Sylla A, Diallo MS, et al. (2006b). Cancer Epidemiol Biomarkers Prev 15:823–6

    Article  PubMed  CAS  Google Scholar 

  • Sidransky D, Hollstein M. (1996). Annu Rev Med 47:285–301

    Article  PubMed  CAS  Google Scholar 

  • Sieber SM, Correa P, Dalgard DW, Adamson RH. (1979). Cancer Res 39:4545–54

    PubMed  CAS  Google Scholar 

  • Smela ME, Hamm ML, Henderson PT, Harris CM, Harris TM, Essigmann JM. (2002). Proc Natl Acad Sci USA 99:6655–60

    Article  PubMed  CAS  Google Scholar 

  • Sun Z, Lu P, Gail MH, Pee D, Zhang Q, et al. (1999). Hepatology 30:379–83

    Article  PubMed  CAS  Google Scholar 

  • Thorgeirsson SS, Grisham JW. (2002). Nat Genet 31:339–46

    Article  PubMed  CAS  Google Scholar 

  • Thorgeirsson UP, Dalgard DW, Reeves J, Adamson RH. (1994). Regul Toxicol Pharmacol 19:130–51

    Article  PubMed  CAS  Google Scholar 

  • Thorgeirsson SS, Lee JS, Grisham JW. (2006). Hepatology 43:S145–50

    Article  PubMed  CAS  Google Scholar 

  • Tilak TB. (1975). Food Cosmet Toxicol 13:247–9

    Article  PubMed  CAS  Google Scholar 

  • Van der Zijden ASM, Koelensmid WAAB, Boldingh J, Barrett CB, Ord WO, Philp J. (1962). Nature 195:1060–2

    Article  Google Scholar 

  • Van Rensburg SJ, Cook-Mozaffari P, Van Schalkwyk DJ, Van der Watt JJ, Vincent TJ, Purchase IF. (1985). Br J Cancer 51:713–26

    Article  PubMed  Google Scholar 

  • Vatanasapt V, Martin N, Sriplung H, Chindavijak K, Sontipong S, et al. (1995). Cancer Epidemiol Biomarkers Prev 4:475–83

    PubMed  CAS  Google Scholar 

  • Wang JS, Groopman JD. (1998). Biomarkers for Carcinogen Exposure: Tumor Initiation. Washington, DC: Taylor & Francis. pp. 145–66

    Google Scholar 

  • Wang JS, Qian GS, Zarba A, He X, Zhu YR, et al. (1996a). Cancer Epidemiol Biomarkers Prev 5:253–61

    PubMed  CAS  Google Scholar 

  • Wang LY, Hatch M, Chen CJ, Levin B, You SL, et al. (1996b). Int J Cancer 67:620–5

    Article  PubMed  CAS  Google Scholar 

  • Wang XW, Hussain SP, Huo TI, Wu CG, Forgues M, et al. (2002). Toxicology 181–182:43–7

    Article  PubMed  Google Scholar 

  • Wild CP, Turner PC. (2002). Mutagenesis 17:471–81

    Article  PubMed  CAS  Google Scholar 

  • Wild CP, Hudson GJ, Sabbioni G, Chapot B, Hall AJ, et al. (1992). Cancer Epidemiol Biomarkers Prev 1:229–34

    PubMed  CAS  Google Scholar 

  • Williams DE, Orner G, Willard KD, Tilton S, Hendricks JD, et al. (2009). Comp Biochem Physiol C Toxicol Pharmacol 149:175–81

    Article  PubMed  Google Scholar 

  • Wogan GN, Newberne PM. (1967). Cancer Res 27:2370–6

    PubMed  CAS  Google Scholar 

  • Yeh FS, Shen KN. (1986). Epidemiology and early diagnosis of primary liver cancer in China. Adv. Cancer Res. 47:297–329

    Article  Google Scholar 

  • Yeh FC, Chang CL, Liu WS. (1986). Ma Zui Xue Za Zhi 24:216–21

    PubMed  CAS  Google Scholar 

  • Yeh FS, Yu MC, Mo CC, Luo S, Tong MJ, Henderson BE. (1989). Cancer Res 49:2506–9

    PubMed  CAS  Google Scholar 

  • Yu MW, Lien JP, Chiu YH, Santella RM, Liaw YF, Chen CJ. (1997). J Hepatol 27:320–30

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by grants P01 ES006052 and P30 ES003819 from the USPHS.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John D. Groopman .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Groopman, J.D., Wogan, G.N. (2011). Aflatoxin and Hepatocellular Carcinoma. In: Penning, T. (eds) Chemical Carcinogenesis. Current Cancer Research. Humana Press. https://doi.org/10.1007/978-1-61737-995-6_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-61737-995-6_6

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61737-994-9

  • Online ISBN: 978-1-61737-995-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics