The Molecular Pathogenesis of Aflatoxin with Hepatitis B Virus-Infection in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and represents the third cause of mortality among deaths from cancer (Semela & Heim, 2011; EI-Serag & Rudolph, 2007; Yuen et al, 2009; Lodato et al, 2006; Hainaut & Boyle, 2008). There are upwards of 600, 000 new cases each year in Asia and sub-Saharan Africa, where populations suffer both from a high prevalence of hepatitis B virus (HBV) infection and largely uncontrolled aflatoxin exposure in food, and more than 200, 000 HCC-related deaths annually in the People’s Republic of China alone (Kew, 2002; Wang et al, 2002). Aflatoxins may play a causative role in 5%-28% of all global HCC cases (Liu & Wu, 2010). Aflatoxin is a kind of mycotoxins produced by the mold Aspergillus flavus, which can be found in legumes, corns, soybeans, rice, milk, and cheese throughout their lives. Aflatoxin B1 (AFB1) is regarded as a class I carcinogen by the World Health Organization (Henry et al, 2001; López et al, 2002). Aflatoxin B1, the most commonly occurring and potent of the aflatoxins is associated with a specific AGG to AGT transversion mutation at codon 249 of the p53 gene in human HCC, providing mechanistic support to a causal link between exposure and disease (Goldman & Shields, 2003; Sugimura, 2000; Wild & Montesano, 2009). Prospective epidemiological studies have shown a more than multiplicative interaction between HBV and aflatoxins in terms of HCC risk. In this chapter, the available evidence for the mechanism of aflatoxin with HBV-infection in HCC will be reviewed.