Determinants of formation of aflatoxin-albumin adducts: a seven-township study in Taiwan.

School of Public Health, National Defense Medical Center, School of Public Health, No. 161, Section 6, Min-Chuan East Road, Taipei 114, Taiwan, Republic of China.
British Journal of Cancer (Impact Factor: 5.08). 11/2002; 87(9):966-70. DOI: 10.1038/sj.bjc.6600584
Source: PubMed

ABSTRACT Dietary exposure to aflatoxins is one of the major risk factors for hepatocellular carcinoma. Individual susceptibility to aflatoxin-induced hepatocarcinogenesis may be modulated by both genetic and environmental factors affecting metabolism. A cross-sectional study was performed to evaluate determinants of the formation of aflatoxin covalently bound to albumin (AFB1-albumin adducts). A total of 474 subjects who were free of liver cancer and cirrhosis and were initially selected as controls for previous case-control studies of aflatoxin-induced hepatocarcinogenesis in Taiwan, were employed in this study. Aflatoxin-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen and antibodies to hepatitis C virus by enzyme immunoassay, as well as genotypes of glutathione S-transferase M1-1 and T1-1 by polymerase chain reaction. The detection rate of AFB1-albumin adducts was significantly higher in males (42.5%) than in females (21.6%) (multivariate-adjusted odds ratio=2.6, 95% confidence interval=1.4-5.0). The formation of detectable albumin adducts was moderately higher in hepatitis B surface antigen carriers (42.8%) than in non-carriers (36.6%) (multivariate-adjusted odds ratio=1.4, 95% confidence interval=1.0-2.1). In addition, the detection rate of AFB1-albumin adducts tended to increase with the increasing number of null genotypes of glutathione S-transferase M1-1 and glutathione S-transferase T1-1. In conclusion, this cross-sectional study has assessed the relative contributions of environmental exposure and host susceptibility factors in the formation of AFB1-albumin adducts in a well characterised Chinese adult population. This study further emphasises the necessity to reduce aflatoxin exposure in people living in an area endemic for chronic hepatitis B virus infection.

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    ABSTRACT: Aflatoxins are a group of mycotoxins produced by Aspergillus flavus and Aspergillus parasiticus . They are potent inducers of hepatotoxicity. Those toxic compounds are ubiquitously found in food commodities such as nuts, cereals, spices and milks and dairy products. Aflatoxin B1 (AFB1) has been classified by the International Agency for Research on Cancer (IARC) as Group 1 carcinogen. Once AFB1 is ingested by humans, it is metabolized by liver enzymes into many metabolites. The study aimed to estimate the hepatotoxicity of AFB1 in workers occupationally exposed to wheat flour dust. Statistical analysis of the results revealed that Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), Alkaline phosphates (ALP) levels in the exposed workers were significantly higher compared to their controls. In the exposed workers, there were significant correlations between AFB1/Alb and the duration of exposure, and between the levels of AST and ALT and the level of AFB1/Alb. The present study concluded that the serum AFB1/Alb was significantly correlated with the duration of exposure in workers exposed to wheat flour dust, and this serum level has hepatotoxic effects in the exposed workers
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    ABSTRACT: Known causes of hepatocellular carcinoma (HCC) are chronic hepatitis B virus (HBV) infection; chronic hepatitis C virus (HCV) infection; dietary exposure to the fungal toxin, aflatoxin B1 (AFB1); cirrhosis, whatever its cause; the metobolic syndrome; hepatic iron overload and a number of rare inherited metabolic diseases. Of these, HBV and AFB1 are the predominant risk factors in those resource-poor countries in Eastern and South-Eastern Asia, the Western Pacific islands, and sub-Saharan Africa that have the highest incidences of the tumour. Closer analysis reveals that the association between exposure to AFB1 and the development of HCC has been reported almost exclusively in countries in which chronic HBV infection is endemic. This is a chance finding, although the possibility that AFB1 is hepatocarcinogenic only in the presence of HBV has been mooted. Chronic HBV infection is more common in rural areas of sub-Saharan Africa and exposure to AFB1 is virtually confined to these areas. Black patients in sub-Saharan Africa and Chinese patients in the Asian-Pacific region with HCC are appreciably younger than patients elsewhere in the world, which could be explained, at least in part, by synergism between the hepatocarcinogenic properties of the two risk factors. Such an interaction may also contribute to the very high incidence of HCC in these regions and to its higher frequency in rural than in urban dwellers in the African sub-continent.
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    ABSTRACT: Due to the possible involvement of Glutathione S-transferase Mu-1 (GSTM1) and Glutathione S-transferase theta-1 (GSTT1) in the detoxification of environmental carcinogens, environmental toxins, and oxidative stress products, genetic polymorphisms of these two genes may play important roles in the susceptibility of human being to hepatocellular carcinoma. However, the existing research results are not conclusive. A systematic literature search using databases (PubMed, Scopus, Embase, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Wanfang Data, etc.) for the eligible studies meeting the inclusion criteria including case-control studies or cohort studies is evaluated using an updated systematic meta-analysis. Significant increase in the risk of HCC in the Chinese population is found in GSTM1 null genotype (OR = 1.47, 95% CI: 1.21 to 1.79, P<0.001) and GSTT1 null genotype (OR = 1.38, 95% CI: 1.14 to 1.65, P<0.001). Analysis using the random-effects model found an increased risk of HCC in GSTM1-GSTT1 dual null population (OR = 1.79, 95% CI: 1.26 to 2.53, P<0.001). In addition, subgroup analyses showed a significant increase in the association of GST genetic polymorphisms (GSTM1, GSTT1, and GSTM1-GSTT1) with HCC in southeast and central China mainland. However, available data collected by this study fail to show an association between GST genetic polymorphisms and HCC in people from the Taiwan region (for GSTM1: OR = 0.78, 95% CI: 0.60 to 1.01, P = 0.06; for GSTT1: OR = 0.94, 95% CI: 0.78 to 1.14, P = 0.546; for GSTM1-GSTT1: OR = 1.04, 95% CI: 0.81 to 1.32, P = 0.77). Sensitivity analysis and publication bias diagnostics confirmed the reliability and stability of this meta-analysis. Our results indicate that both GSTM1 and GSTT1 null genotypes are associated with an increased HCC risk in Chinese population. Peoples with dual null genotypes of GSTM1-GSTT1 are more susceptible to developing HCC. In conclusion, GST genetic polymorphisms play vital roles in the development of HCC in the Chinese population.
    PLoS ONE 01/2013; 8(2):e57043. · 3.73 Impact Factor

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