Aflatoxin B1-induced hepatocellular carcinoma in developing countries: Geographical distribution, mechanism of action and prevention (Review)

  • Authors:
    • Abdu Selim Hamid
    • Isaias Goitom Tesfamariam
    • Yucheng Zhang
    • Zhen Gui Zhang
  • View Affiliations

  • Published online on: January 31, 2013     https://doi.org/10.3892/ol.2013.1169
  • Pages: 1087-1092
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Abstract

Hepatocellular carcinoma (HCC) is the most well-known primary liver malignancy worldwide. Its incidence is rising at alarming rates and has become a public concern globally. It is more frequent in developing countries than in industrialized countries with respect to geographical variation, ethnic disparities and socioeconomic status. Dietary exposure to aflatoxins is among the major HCC risk factors. Aflatoxin B1, which is a genotoxic hepatocarcinogen, which presumptively causes cancer by inducing DNA adducts leading to genetic changes in target liver cells. AFB1 is metabolized by cytochrome-P450 enzymes to the reactive intermediate AFB1-8, 9 epoxide (AFBO) which binds to liver cell DNA, resulting in DNA adducts. DNA adducts interact with the guanine bases of liver cell DNA and cause a mutational effect in the P53 tumor suppressor gene at the codon 249 hotspot in exon 7, which may lead to HCC. Approximately 4.5 billion of the world's population is exposed to aflatoxin‑contaminated food, particularly in low‑income countries. Prevention involves treating crops that are susceptible to fungal contamination, appropriate handling of foodstuffs and the use of chemopreventive intervention. Moreover, an integrated network collaboration of different sectors, including public health, agricultural departments and mass media, is required to ensure effective food regulation systems so as to minimize the contamination of food by aflatoxins.

References

1 

Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet. 362:1907–1917. 2003. View Article : Google Scholar

2 

Lord R, Suddle A and Ross PJ: Emerging strategies in the treatment of advanced hepatocellular carcinoma: the role of targeted therapies. Int J Clin Pract. 65:182–188. 2011. View Article : Google Scholar : PubMed/NCBI

3 

El-Serag HB and Rudolph KL: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI

5 

El-Serag HB and Mason AC: Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 340:745–750. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Altekruse SF, McGlynn KA and Reichman ME: Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 27:1485–1491. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Nguyen MH, Whittemore AS, Garcia RT, et al: Role of ethnicity in risk for hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis. Clin Gastroenterol Hepatol. 2:820–824. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Farazi PA and DePinho RA: Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer. 6:674–687. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Ward E, Jemal A, Cokkinides V, et al: Cancer disparities by race/ethnicity and socioeconomic status. CA Cancer J Clin. 54:78–93. 2004. View Article : Google Scholar

10 

McCracken M, Olsen M, Chen MS Jr, et al: Cancer incidence, mortality, and associated risk factors among Asian Americans of Chinese, Filipino, Vietnamese, Korean, and Japanese ethnicities. CA Cancer J Clin. 57:190–205. 2007. View Article : Google Scholar

11 

Röcken C and Carl-McGrath S: Pathology and pathogenesis of hepatocellular carcinoma. Dig Dis. 19:269–278. 2001.

12 

McGlynn KA and London WT: Epidemiology and natural history of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol. 19:3–23. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Sherman M: Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis. 25:143–154. 2005. View Article : Google Scholar : PubMed/NCBI

14 

London WT, Evans AA, McGlynn K, et al: Viral, host and environmental risk factors for hepatocellular carcinoma: a prospective study in Haimen City, China. Intervirology. 38:155–161. 1995.PubMed/NCBI

15 

Chen CJ, Yu MW and Liaw YF: Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastroenterol Hepatol. 12:S294–S308. 1997. View Article : Google Scholar : PubMed/NCBI

16 

Madden CR, Finegold MJ and Slagle BL: Altered DNA mutation spectrum in aflatoxin b1-treated transgenic mice that express the hepatitis B virus x protein. J Virol. 76:11770–11774. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Li Y, Su JJ, Qin LL, Yang C, Ban KC and Yan RQ: Synergistic effect of hepatitis B virus and aflatoxin B1 in hepatocarcinogenesis in tree shrews. Ann Acad Med Singapore. 28:67–71. 1999.PubMed/NCBI

18 

Montalto G, Cervello M, Giannitrapani L, Dantona F, Terranova A and Castagnetta LA: Epidemiology, risk factors, and natural history of hepatocellular carcinoma. Ann NY Acad Sci. 963:13–20. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Groopman JD, Scholl P and Wang JS: Epidemiology of human aflatoxin exposures and their relationship to liver cancer. Prog Clin Biol Res. 395:211–222. 1996.PubMed/NCBI

20 

Baydar T, Engin AB, Girgin G, Aydin S and Sahin G: Aflatoxin and ochratoxin in various types of commonly consumed retail ground samples in Ankara, Turkey. Ann Agric Environ Med. 12:193–197. 2005.PubMed/NCBI

21 

Bennett JW and Klich M: Mycotoxins. Clin Microbiol Rev. 16:497–516. 2003. View Article : Google Scholar

22 

Fink-Gremmels J: Mycotoxins: their implications for human and animal health. Vet Q. 21:115–120. 1999. View Article : Google Scholar : PubMed/NCBI

23 

Williams JH, Phillips TD, Jolly PE, Stiles JK, Jolly CM and Aggarwal D: Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr. 80:1106–1122. 2004.

24 

McLean M and Dutton MF: Cellular interactions and metabolism of aflatoxin: an update. Pharmacol Ther. 65:163–192. 1995. View Article : Google Scholar : PubMed/NCBI

25 

Wang JS, Huang T, Su J, et al: Hepatocellular carcinoma and aflatoxin exposure in Zhuqing Village, Fusui County, People’s Republic of China. Cancer Epidemiol Biomarkers Prev. 10:143–146. 2001.PubMed/NCBI

26 

Mardani M, Rezapour S and Rezapour P: Survey of aflatoxins in Kashkineh: A traditional Iranian food. Iran J Microbiol. 3:147–151. 2011.PubMed/NCBI

27 

Banerjee S, Brown KL, Egli M and Stone MP: Bypass of aflatoxin B1 adducts by the Sulfolobus solfataricus DNA polymerase IV. J Am Chem Soc. 133:12556–12568. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Obuseh FA, Jolly PE, Kulczycki A, et al: Aflatoxin levels, plasma vitamins A and E concentrations, and their association with HIV and hepatitis B virus infections in Ghanaians: a cross-sectional study. J Int AIDS Soc. 14:532011. View Article : Google Scholar : PubMed/NCBI

29 

Lewis L, Onsongo M, Njapau H, et al: Aflatoxin contamination of commercial maize products during an outbreak of acute aflatoxicosis in eastern and central Kenya. Environ Health Perspect. 113:1763–1767. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Oyelami OA, Maxwell SM and Adeoba E: Aflatoxins and ochratoxin A in the weaning food of Nigerian children. Ann Trop Paediatr. 16:137–140. 1996.PubMed/NCBI

31 

Egal S, Hounsa A, Gong YY, et al: Dietary exposure to aflatoxin from maize and groundnut in young children from Benin and Togo, West Africa. Int J Food Microbiol. 104:215–224. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Kpodo K, Thrane U and Hald B: Fusaria and fumonisins in maize from Ghana and their co-occurrence with aflatoxins. Int J Food Microbiol. 61:147–157. 2000. View Article : Google Scholar : PubMed/NCBI

33 

Awuah RT and Kpodo KA: High incidence of Aspergillus flavus and aflatoxins in stored groundnut in Ghana and the use of a microbial assay to assess the inhibitory effects of plant extracts on aflatoxin synthesis. Mycopathologia. 134:109–114. 1996.

34 

Sugimura T: Nutrition and dietary carcinogens. Carcinogenesis. 21:387–395. 2000. View Article : Google Scholar

35 

Sutandyo N: Nutritional carcinogenesis. Acta Med Indones. 42:36–42. 2010.

36 

Sharma RA and Farmer PB: Biological relevance of adduct detection to the chemoprevention of cancer. Clin Cancer Res. 10:4901–4912. 2004. View Article : Google Scholar : PubMed/NCBI

37 

Martin J and Dufour JF: Tumor suppressor and hepatocellular carcinoma. World J Gastroenterol. 14:1720–1733. 2008. View Article : Google Scholar : PubMed/NCBI

38 

Jackson PE, Kuang SY, Wang JB, et al: Prospective detection of codon 249 mutations in plasma of hepatocellular carcinoma patients. Carcinogenesis. 24:1657–1663. 2003. View Article : Google Scholar : PubMed/NCBI

39 

Bressac B, Kew M, Wands J and Ozturk M: Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature. 350:429–431. 1991. View Article : Google Scholar : PubMed/NCBI

40 

Montesano R, Hainaut P and Wild CP: Hepatocellular carcinoma: from gene to public health. J Natl Cancer Inst. 89:1844–1851. 1997. View Article : Google Scholar : PubMed/NCBI

41 

Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ and Harris CC: Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature. 350:427–428. 1991. View Article : Google Scholar : PubMed/NCBI

42 

Ozturk M: p53 mutation in hepatocellular carcinoma after aflatoxin exposure. Lancet. 338:1356–1359. 1991. View Article : Google Scholar : PubMed/NCBI

43 

Stern MC, Umbach DM, Yu MC, London SJ, Zhang ZQ and Taylor JA: Hepatitis B, aflatoxin B(1), and p53 codon 249 mutation in hepatocellular carcinomas from Guangxi, People’s Republic of China, and a meta-analysis of existing studies. Cancer Epidemiol Biomarkers Prev. 10:617–625. 2001.PubMed/NCBI

44 

Nogueira JA, Ono-Nita SK, Nita ME, et al: 249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients. BMC Cancer. 9:2042009. View Article : Google Scholar : PubMed/NCBI

45 

Wang JS and Groopman JD: DNA damage by mycotoxins. Mutat Res. 424:167–181. 1999. View Article : Google Scholar : PubMed/NCBI

46 

Eaton DL and Gallagher EP: Mechanisms of aflatoxin carcinogenesis. Annu Rev Pharmacol Toxicol. 34:135–172. 1994. View Article : Google Scholar : PubMed/NCBI

47 

Gallagher EP, Kunze KL, Stapleton PL and Eaton DL: The kinetics of aflatoxin B1 oxidation by human cDNA-expressed and human liver microsomal cytochromes P450 1A2 and 3A4. Toxicol Appl Pharmacol. 141:595–606. 1996. View Article : Google Scholar : PubMed/NCBI

48 

Ilic Z, Crawford D, Vakharia D, Egner PA and Sell S: Glutathione-S-transferase A3 knockout mice are sensitive to acute cytotoxic and genotoxic effects of aflatoxin B1. Toxicol Appl Pharmacol. 242:241–246. 2010. View Article : Google Scholar : PubMed/NCBI

49 

Dash B, Afriyie-Gyawu E, Huebner HJ, et al: Determinants of the variability of aflatoxin-albumin adduct levels in Ghanaians. J Toxicol Environ Health A. 70:58–66. 2007. View Article : Google Scholar : PubMed/NCBI

50 

Eaton DL, Bammler TK and Kelly EJ: Interindividual differences in response to chemoprotection against aflatoxin-induced hepatocarcinogenesis: implications for human biotransformation enzyme polymorphisms. Adv Exp Med Biol. 500:559–576. 2001. View Article : Google Scholar

51 

Kirk GD, Turner PC, Gong Y, et al: Hepatocellular carcinoma and polymorphisms in carcinogen-metabolizing and DNA repair enzymes in a population with aflatoxin exposure and hepatitis B virus endemicity. Cancer Epidemiol Biomarkers Prev. 14:373–379. 2005. View Article : Google Scholar : PubMed/NCBI

52 

Smela ME, Currier SS, Bailey EA and Essigmann JM: The chemistry and biology of aflatoxin B(1): from mutational spectrometry to carcinogenesis. Carcinogenesis. 22:535–545. 2001. View Article : Google Scholar : PubMed/NCBI

53 

Wild CP and Turner PC: The toxicology of aflatoxins as a basis for public health decisions. Mutagenesis. 17:471–481. 2002. View Article : Google Scholar : PubMed/NCBI

54 

Guengerich FP, Johnson WW, Shimada T, Ueng YF, Yamazaki H and Langouët S: Activation and detoxication of aflatoxin B1. Mutat Res. 402:121–128. 1998. View Article : Google Scholar : PubMed/NCBI

55 

Sabbioni G, Skipper PL, Büchi G and Tannenbaum SR: Isolation and characterization of the major serum albumin adduct formed by aflatoxin B1 in vivo in rats. Carcinogenesis. 8:819–824. 1987. View Article : Google Scholar : PubMed/NCBI

56 

Anand P, Kunnumakkara AB, Sundaram C, et al: Cancer is a preventable disease that requires major lifestyle changes. Pharm Res. 25:2097–2116. 2008. View Article : Google Scholar : PubMed/NCBI

57 

Wild CP and Hall AJ: Primary prevention of hepatocellular carcinoma in developing countries. Mutat Res. 462:381–393. 2000. View Article : Google Scholar : PubMed/NCBI

58 

Gescher AJ, Sharma RA and Steward WP: Cancer chemoprevention by dietary constituents: a tale of failure and promise. Lancet Oncol. 2:371–379. 2001. View Article : Google Scholar : PubMed/NCBI

59 

Brahmi D, Bouaziz C, Ayed Y, Ben Mansour H, Zourgui L and Bacha H: Chemopreventive effect of cactus Opuntia ficus indica on oxidative stress and genotoxicity of aflatoxin B1. Nutr Metab (Lond). 8:732011.

60 

Peterson S, Lampe JW, Bammler TK, Gross-Steinmeyer K and Eaton DL: Apiaceous vegetable constituents inhibit human cytochrome P-450 1A2 (hCYP1A2) activity and hCYP1A2-mediated mutagenicity of aflatoxin B1. Food Chem Toxicol. 44:1474–1484. 2006. View Article : Google Scholar : PubMed/NCBI

61 

Miyata M, Takano H, Guo LQ, Nagata K and Yamazoe Y: Grapefruit juice intake does not enhance but rather protects against aflatoxin B1-induced liver DNA damage through a reduction in hepatic CYP3A activity. Carcinogenesis. 25:203–209. 2004. View Article : Google Scholar : PubMed/NCBI

62 

Cavin C, Marin-Kuan M, Langouët S, et al: Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver. Food Chem Toxicol. 46:1239–1248. 2008. View Article : Google Scholar : PubMed/NCBI

63 

Gross-Steinmeyer K, Stapleton PL, Tracy JH, Bammler TK, Strom SC and Eaton DL: Sulforaphane- and phenethyl isothiocyanate-induced inhibition of aflatoxin B1-mediated genotoxicity in human hepatocytes: role of GSTM1 genotype and CYP3A4 gene expression. Toxicol Sci. 116:422–432. 2010. View Article : Google Scholar

64 

Sotomayor RE, Washington M, Nguyen L, Nyang’anyi R, Hinton DM and Chou M: Effects of intermittent exposure to aflatoxin B1 on DNA and RNA adduct formation in rat liver: dose-response and temporal patterns. Toxicol Sci. 73:329–338. 2003. View Article : Google Scholar : PubMed/NCBI

65 

McGlynn KA, Hunter K, LeVoyer T, et al: Susceptibility to aflatoxin B1-related primary hepatocellular carcinoma in mice and humans. Cancer Res. 63:4594–4601. 2003.PubMed/NCBI

66 

Turner PC, Sylla A, Gong YY, et al: Reduction in exposure to carcinogenic aflatoxins by postharvest intervention measures in west Africa: a community-based intervention study. Lancet. 365:1950–1956. 2005. View Article : Google Scholar : PubMed/NCBI

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April 2013
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APA
Hamid, A.S., Tesfamariam, I.G., Zhang, Y., & Zhang, Z.G. (2013). Aflatoxin B1-induced hepatocellular carcinoma in developing countries: Geographical distribution, mechanism of action and prevention (Review). Oncology Letters, 5, 1087-1092. https://doi.org/10.3892/ol.2013.1169
MLA
Hamid, A. S., Tesfamariam, I. G., Zhang, Y., Zhang, Z. G."Aflatoxin B1-induced hepatocellular carcinoma in developing countries: Geographical distribution, mechanism of action and prevention (Review)". Oncology Letters 5.4 (2013): 1087-1092.
Chicago
Hamid, A. S., Tesfamariam, I. G., Zhang, Y., Zhang, Z. G."Aflatoxin B1-induced hepatocellular carcinoma in developing countries: Geographical distribution, mechanism of action and prevention (Review)". Oncology Letters 5, no. 4 (2013): 1087-1092. https://doi.org/10.3892/ol.2013.1169