Aflatoxins as risk factors for primary hepatocellular carcinoma in humans

Primary hepatocellular carcinoma is among the most common forms of cancer on a global basis. Incidence of the disease varies greatly in different areas of the world. This wide variation in incidence suggests the possible involvement of environmental etiological factors, and much research has been devoted to their identification. Extensive evidence is available to indicate that infection by the hepatitis B virus constitutes a major risk factor for primary hepatocellular carcinoma. Because many synthetic and naturally occurring organic chemicals have been shown to induce liver cancer in experimental animals, those to which humans are known to have been exposed have been extensively studied with respect to their possible significance as risk factors for primary hepatocellular carcinoma. Particular emphasis has been placed on aflatoxins because of their widespread occurrence as food contaminants and their high potency as liver carcinogens for a large number of experimental animals, including subhuman primates. Epidemiological surveys have revealed a strong statistical association between aflatoxin ingestion and primary hepatocellular carcinoma incidence in Africa and Asia. The International Agency for Research on Cancer has recently determined that the combined experimental and epidemiological evidence was sufficient to designate aflatoxins as human carcinogens. The combined epidemiological and laboratory evidence suggests that primary hepatocellular carcinoma is of multifactorial origin, with possible interplay between viral and chemical agents acting alone or in combination in its causation. Recently developed methods that permit individual monitoring of aflatoxin exposure as well as hepatitis B virus infection and also genetic damage caused by these agents are being applied in the design of molecular and biochemical epidemiological studies of the etiology of the disease. In addition, aflatoxins have been shown to activate cellular proto-oncogenes in experimentally induced primary hepatocellular carcinoma in animals; this information may provide a means of determining their importance as carcinogens in humans.