Abstract PL02-02 Mycotoxins are fungal metabolites which commonly contaminate the human food supply, particularly cereals (e.g. maize (corn), wheat, barley and oats), oilseeds (e.g. groundnuts (peanuts)) and tree nuts. Estimates are that around 25% of food worldwide contains these toxins. The mycotoxins of most importance from a human health perspective are aflatoxins, fumonisins, ochratoxin A, tricothecenes and zearalenone. Exposure to aflatoxins and fumonisins, both of which are carcinogenic, occurs predominantly in developing countries. This is due to a combination of factors, including the climatic conditions which promote crop stress, fungal growth and toxin production during cultivation and storage; the reliance on a few dietary staple foods; inadequate food sufficiency, translating to consumption of contaminated food; and the absence of regulation, or implementation of regulations, to control mycotoxin levels in the food supply. At the same time, understanding the human health effects of mycotoxins has been hampered, at least in part, by the absence of accurate exposure measurements. In response, biomarkers offer to improve exposure assessment at the individual level. These same biomarkers can be used to evaluate potential approaches to reduce mycotoxin exposure. Aflatoxins have been associated with increased liver cancer risk in interaction with chronic hepatitis B virus (HBV) infection, but the underlying molecular mechanisms remain ill-defined. Genetic polymorphisms in genes coding for aflatoxin metabolising enzymes and DNA repair enzymes were associated with an altered cancer risk1,2 and earlier data suggested that HBV infection could alter expression of some of these metabolising enzymes3. In West Africa there is a high prevalence and level of dietary exposure to aflatoxins, with >90% of the individuals having detectable blood aflatoxin-albumin adduct4. Exposure is life-long, beginning in utero, reducing during breastfeeding, but increasing markedly at weaning. This exposure early in life in West Africa has been associated with a striking impairment of growth in young children5-8. Exposure was also associated with a decrease in salivary IgA levels9. Growth and immune impairment could therefore be critical in pre-disposing children to the infections, including HBV, that result in the high morbidity and mortality in these populations. In parallel, to the studies of disease aetiology, we evaluated a simple post-harvest intervention in Guinea to reduce aflatoxin contamination of the groundnut crop. This involved sun-drying the crop on mats prior to storage; the use of natural fibre bags for storage; the use of wooden pallets to keep the bags off the moist earth in the storage facilities and the application of insecticide on the floor of the facility. This intervention resulted in a >50% mean reduction in aflatoxin-albumin adducts in subjects in the intervention villages five months post-harvest10. In addition, around 20% of subjects in the intervention villages had no detectable aflatoxin-albumin biomarker in their serum compared to less than 3% in the control villages. This demonstrates that relatively simple prevention approaches can make a significant impact on aflatoxin exposure when implemented at the small subsistence farm level. This primary prevention compares well with the alternative approach of chemoprevention using oltipraz, chlorophyllin, green tea or broccoli tea as demonstrated in studies in aflatoxin-exposed individuals in the People’s Republic of China11. More recently the use of absorbent clays in the diet in Ghana has been shown to reduce aflatoxin biomarker levels12. Overall the prevention of hepatocellular carcinoma in developing countries depends on reducing chronic infection with hepatitis B or C viruses as well as a reduction in aflatoxin exposure. It is also notable that the health effects of aflatoxin exposure may extend well-beyond liver cancer if the associations with impaired growth and immunity are causal. This would significantly change the priority assigned to tackling this environmental toxin. Fumonisins are predominantly found in maize. These toxins have been associated with squamous cell carcinoma of the oesophagus in parts of southern Africa and People’s Republic of China and, more recently, with a high incidence of neural tube defects on the Texas-Mexico border. We developed a urinary biomarker for fumonisin exposure and in a study in Mexico showed that tortilla intake, the major source of maize, was correlated with the biomarker13. In the former Transkei region of South Africa a high level of fumonisin exposure was also demonstrated using the urinary biomarker. The effectiveness in reducing fumonisin contamination by hand-washing and sorting maize kernels prior to cooking was evaluated using the biomarker in a study of subsistence farming families. In summary, mycotoxins are common in much of the food supply of the developing world. However, the adverse health effects of these chronic exposures are not fully understood. The ability to measure exposure permits both aetiologic and intervention studies to be conducted in the future. Finally, in assessing the benefits of interventions, the complex range of adverse health effects resulting from mycotoxin exposure needs to be taken into account. Citation Information: Cancer Prev Res 2008;1(7 Suppl):PL02-02.
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Dec 9, 2024
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