Aflatoxin: A major risk factor for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is ranked among the most common leading causes of death from cancers worldwide. Majorly responsible for this is the potent mycotoxin produced by Aspergillus flavus and Aspergillus parasiticus, aflatoxin. The risk factors are included to be hepatitis B and C viruses, HBV and HCV. Molecular mechanisms involved in a flatoxin and HBV/HCV-associated hepatocarcinogenesis include the complex interplay of genetic and epigenetic alterations that help in disrupting normal cellular processes with the action of cancerous traits. As aflatoxin triggers genetic mutations and epigenetic modifications through its activation and production of DNA adducts, while HBV and HCV infections lead to chronic hepatitis, oxidative damage, direct contact with host cellular machinery and favor the development of HCC. Mostly, aflatoxins are ingested through food products contaminated with this toxin, particularly grains and nuts, which are regularly consumed by populations using insanitary agriculture and storage of food. Once inside the body, aflatoxin B1 and similar metabolites have the ability to activate the cellular pathways associated with metabolic activation through cytochrome P450 enzymes that result in the creation of DNA adducts. These adducts lead to mutations within critical tumor suppressor genes like TP53 and activate oncogenes like RAS, causing tumorigenesis. Elucidating the complex molecular crosstalk between aflatoxin exposure and HBV/HCV infections is important for advancing targeted interventions to mitigate the global burden of HCC. This review consolidates the latest findings but sets a course for future research promisingly unravelling the complex interactions between aflatoxin exposure and HBV/HCV infections. It helps pave the way to good clinical outcomes and effective public health strategies as a means of combating hepatocellular carcinoma.