Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei

Rensburg, S.J. Van; Cook-Mozaffari, Paula; Schalkwyk, David; Watt, J. J. van der; Vincent, T J; Purchase, I. F. H.

doi:10.1038/bjc.1985.107

Cited by 292 publications

(157 citation statements)

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“…HCC causes 65% to 75% of all cancer deaths in males and 30% to 55% of cancer deaths in females in Mozambique and some provinces of Southern China. [4][5][6][7] Our results in transgenic mice agree with this epidemiological data. Tumor incidence in male mice, regardless of the genotype, is consistently higher than in female mice.…”

Section: Discussionsupporting

confidence: 87%

“…[1][2][3] It causes 65% to 75% of all cancer deaths in males and 30% to 55% of cancer deaths in females in Mozambique and some provinces of Southern China. [4][5][6][7] Epidemiological studies have identified infection with hepatitis B or C virus and contamination of grains with aflatoxin B 1 (AFB 1 ) as major and possibly synergistic risk factors in these areas. 2 Individuals with chronic hepatitis B virus (HBV) infection have a 200-fold greater risk of developing HCC than age-matched noninfected controls.…”

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confidence: 99%

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Hepatitis B injury, male gender, aflatoxin, and p53 expression each contribute to hepatocarcinogenesis in transgenic mice†

Ghebranious

Sell

1998

Hepatology

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The objective of the present study is to develop experimental models in mice to study the role of the four major risk factors for development of hepatocellular carcinoma (HCC) in humans. The major risk factors are: hepatitis B infection, male gender, aflatoxin exposure, and p53 gene loss or mutation. HCC is the predominant cause of cancer mortality of males in Sub-Saharan Africa and Southern China. 1-3 It causes 65% to 75% of all cancer deaths in males and 30% to 55% of cancer deaths in females in Mozambique and some provinces of Southern China. [4][5][6][7] Epidemiological studies have identified infection with hepatitis B or C virus and contamination of grains with aflatoxin B 1 (AFB 1 ) as major and possibly synergistic risk factors in these areas. 2 Individuals with chronic hepatitis B virus (HBV) infection have a 200-fold greater risk of developing HCC than age-matched noninfected controls. 8 Of particular interest in regard to the relative importance of chronic hepatitis and AFB 1 is the geographical distribution of liver cancer in China. It is very uneven and does not follow closely the incidence of chronic hepatitis, but does follow the areas of aflatoxin contamination of ground nuts. 9

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Section: Discussionsupporting

confidence: 87%

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confidence: 99%

Hepatitis B injury, male gender, aflatoxin, and p53 expression each contribute to hepatocarcinogenesis in transgenic mice†

Ghebranious

Sell

1998

Hepatology

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“…68 Specific P450 enzymes in the liver metabolize aflatoxin into a reactive oxygen species (aflatoxin-8,9-epoxide), which may then bind to proteins and cause acute toxicity (aflatoxicosis) or to DNA to cause lesions that over time increase the risk of HCC. 69 A causative role for aflatoxins in hepatocarcinogenesis in humans has been strongly suggested based on various epidemiological data. The degree of food contamination by aflatoxins and HCC incidence are closely and significantly correlated by Lin et al 1977.…”

Section: Role Of Aflatoxin B Causes Hepatocellular Carcinoma In Indiamentioning

confidence: 99%

Risk Factors for Hepatocellular Carcinoma in India

Kar

2014

Journal of Clinical and Experimental Hepatology

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Hepatocellular carcinoma (HCC) is an important cause of death all over the world, more so in Asia and Africa. The representative data on epidemiology of HCC in India is very scanty and cancer is not a reportable disease in India and the cancer registries in India are mostly urban. 45 million people who are suffering from chronic Hepatitis B virus (HBV) infection and approximately 15 million people who are afflicted with chronic Hepatitis C virus (HCV) infection in India. HBV and HCV infection is considered an important etiologic factor in HCC. Positive association between HCC and consumption of alcohol where alcohol contribute as a cofactor for hepatotoxins and hepatitis viruses. Aflatoxin contamination in the diets, Hepatitis B virus infection and liver cirrhosis in Andhra Pradesh, India and direct chronic exposure to aflatoxins was shown to cause liver cirrhosis. Cirrhosis of liver of any cause lead to develop about 70%-90% of HCC. Aflatoxin interact synergistically with Hepatitis B virus (HBV)/Hepatitis C virus (HCV) infection which increase the risk of HCC. HBV infection, HBV infection with Aflatoxin exposure, viral infection and alcohol consumption leading to overt cirrhosis of the liver, alcohol consumption leading to cirrhosis of the liver with viral infection are the predominant risk factor for the development of HCC. HCV and alcohol are also associated with HCC in India. Indians develop diabetes at younger age, Asians have strong genetic susceptibility for type II diabetes. Diabetes mellitus is identified as a risk factor for HCC. Prevention of viral infection by universal vaccination against hepatitis virus, HCC surveillance program, preventing alcoholic liver diseases, fungal contamination of grains and ground crops to prevent basically Aflatoxin exposure are important measures to prevent liver diseases and HCC among those at risk. ( J CLIN EXP HEPATOL 2014;4:S34-S42)

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“…[1][2][3] Roughly two thirds of all cancer deaths in males and one third of cancer deaths in females in these areas are caused by HCC. [4][5][6][7] The high incidence of HCC is closely associated with liver injury caused by hepatitis B or C virus and consumption of food contaminated with aflatoxin (AFB1). 2,8,9 In the HCCs found in these high-risk areas a mutation in codon 249 of the p53 gene occurs with high frequency: 58% of HCCs from Qidong, China, and 53% from Mozambique.…”

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confidence: 99%

The mouse equivalent of the human p53ser249 mutation p53ser246 enhances aflatoxin hepatocarcinogenesis in hepatitis B surface antigen transgenic and p53 heterozygous null mice

Ghebranious

Sell

1998

Hepatology

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The relative contribution to development of hepatocellular carcinoma of the mouse equivalent to the human p53ser249 mutation, found in human hepatocellular carcinoma associated with aflatoxin (AFB1) exposure, is compared with other major risk factors in a transgenic mouse model. Transgenic p53ser246 mice, expressing the mutant protein gene under the control of a truncated albumin promoter, were bred to mice lacking p53 (p53؊/؊) and to transgenic mice expressing hepatitis B surface antigen (HBsAg). AFB1 hepatocarcinogenesis was then determined in offspring with single or multiple risk factors by determination of the numbers of high-grade hepatic tumors at 13 months of age. In AFB1-treated male mice, expression of the p53ser246 mutation increases the incidence of high-grade tumors from 0% to 14% in HBsAg-negative, p53؉/؉ (wildtype homozygous) control mice; from 14% to 71% in HBsAg-negative, p53؉/؊ (wild-type heterozygous) mice; and from 62% to 100% in HBsAg-positive, p53؉/؉ mice. Thus, whereas HBsAg expression and AFB1 together are strongly cocarcinogenic, the presence of the p53ser246 mutant not only significantly enhances this cocarcinogenic effect, it also increases tumorigenesis in AFB1-treated p53 heterozygous and homozygous mice not expressing HBsAg. The possibility that the p53ser246 mutant protein may act as a promoting agent for AFB1 hepatocarcinogenesis is discussed. (HEPATOLOGY 1998;27:967-973.)The effect of the mouse equivalent to the human p53 mutation at position 249 resulting in an Arg to Ser mutation is examined in transgenic mouse models replicating the risk factors for development of hepatocellular carcinoma (HCC) in humans. The major cause of cancer mortality in subSaharan Africa and southern China is HCC. 1-3 Roughly two thirds of all cancer deaths in males and one third of cancer deaths in females in these areas are caused by HCC. [4][5][6][7] The high incidence of HCC is closely associated with liver injury caused by hepatitis B or C virus and consumption of food contaminated with aflatoxin (AFB1). 2,8,9 In the HCCs found in these high-risk areas a mutation in codon 249 of the p53 gene occurs with high frequency: 58% of HCCs from Qidong, China, and 53% from Mozambique. There is also a close association of the p53ser249 mutation in HCCs resulting from AFB1 exposure. 1,7 The objective of the work described in this paper is to determine, in transgenic mouse models, the contribution of the specific p53 mutation found in HCC in relationship to the other risk factors for human HCC. The p53ser246 mutation in the mouse corresponds to the p53ser249 mutation in humans. 10 The interaction of the major risk factors for human HCC and the effect of loss and specific mutation of p53 are examined in offspring of transgenic mice expressing the p53ser246 mutation bred to p53 null mice (p53ϩ/Ϫ) and to transgenic mice expressing hepatitis B surface antigen (HBsAg), with and without exposure to AFB1. These conditions duplicate in an animal model the major risk factors for, and the most frequent genetic change in,...

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Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei

Cited by 292 publications

References 41 publications

Hepatitis B injury, male gender, aflatoxin, and p53 expression each contribute to hepatocarcinogenesis in transgenic mice†

Hepatitis B injury, male gender, aflatoxin, and p53 expression each contribute to hepatocarcinogenesis in transgenic mice†

Risk Factors for Hepatocellular Carcinoma in India

The mouse equivalent of the human p53ser249 mutation p53ser246 enhances aflatoxin hepatocarcinogenesis in hepatitis B surface antigen transgenic and p53 heterozygous null mice

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