AFLATOXINS AS RISK-FACTORS FOR HEPATOCELLULAR-CARCINOMA IN HUMANS

On a global basis, primary liver cancer (PLC) is a very prevalent form of cancer. Wide variation of PLC incidence in different areas of the world suggests the involvement of environmental factors in its etiolog y. Two major classes of risk factors have been identified. Extensive e vidence indicates the importance of infection by the hepatitis B virus as a major risk factor for PLC. Because many organic chemicals induce liver cancer in experimental animals, those to which human exposure i s known to occur are also of interest with respect to their possible i nvolvement as risk factors for PLC. Particular emphasis has been place d on aflatoxins because of the frequency with which they occur as food contaminants, together with their potency as liver carcinogens for a large number of experimental animals, including subhuman primates. Oth er mycotoxins, notably sterigmatocystin and fumonisin, also are relati vely potent carcinogens for the liver of animals, but little is known about human exposure to them. Epidemiological surveys carried out over the past 25 years in Asia and Africa have revealed a strong statistic al association between aflatoxin ingestion and PLC incidence. The comb ined experimental and epidemiological evidence has led to designation of aflatoxins as human carcinogens according to International Agency f or Cancer Research critera. Collectively, current evidence strongly su ggests that PLC is of multifactorial origin, with probable interaction s between viral and chemical agents in populations concurrently expose d to both classes of risk factors. Recently developed methods that per mit individual monitoring of aflatoxin exposure, hepatitis B virus inf ection, and genetic damage caused by these agents are being applied in the design of molecular and biochemical epidemiological studies of th e etiology of the disease. Application of this methodology may contrib ute to elucidation of the relative importance of interacting etiologic al agents in different populations.