Peanut butter consumption and hepatocellular carcinoma in Sudan

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with 80% of cases occurring in developing countries in sub-Saharan regions in Africa, South-East Asia and China. The cancer is highly fatal and survival is generally less than 1 year from diagnosis. Clinical records suggest that the incidence of this cancer is high and increasing in Sudan. Major risk factors of HCC have been identified as dietary exposure to aflatoxins, chronic infection with hepatitis B virus (HBV) and other hepatitis viruses and the intake of alcoholic beverages. Climatic conditions, agricultural practices and the dietary patterns in Sudan, as well as in many of the sub-Saharan African countries, are contributing to the contamination of food with aflatoxins and possibly to the incidence of HCC.The aim of this study was to investigate the role of aflatoxins from peanut butter in the etiology of HCC in Sudan, and to substantiate this by studying polymorphisms of potential relevant genes for aflatoxin metabolism. The ultimate goal of this study was to find clues for prevention and control of HCC in Sudan, by investigating the relative importance of aflatoxins (peanut butter intake) and hepatitis infections. Accordingly, implications for agricultural and public health policy can be substantiated.First, an explorative study was conducted among 24 cases and 34 controls. This study confirmed that high amounts of aflatoxins (20 times above the guidelines of the World Health Organization) are present in Sudanese peanut butter and suggested that humid storage conditions might contribute to the risk of HCC. Furthermore, procedures for the main study were tested and adapted.In the main study 150 cases with HCC and 200 controls, matched for sex, were enrolled from West and Central Sudan. In this study, an about four-fold increased risk of HCC was observed among subjects with a high daily consumption of peanut butter. This association was considerably stronger for subjects having genetic polymorphisms of glutathione S-transferase M1 (GSTM1). For the polymorphisms in glutathione S-transferase T1 (GSTT1) and microsomal epoxide hydrolase (EPHX), no association was observed. This might indicate that GSTM1 is a more important rate-limiting factor in the metabolism of aflatoxins. In addition, we observed a positive association between the intake of peanut butter stored in humid storage conditions although less clear than it was in the explorative study. Regarding hepatitis infections, a fifteen-fold increased risk was found for those who had experienced HBV infections.The results of our study point at both exposure to aflatoxins through peanut butter intake and hepatitis B infection as important risk factors of HCC in Sudan. Although hepatitis B infection was a much stronger risk factor as compared to aflatoxins/peanut butter, the latter was almost equally important to public health because of the high prevalence of aflatoxin contamination. About fifty percent of all cases of HCC might be attributable to contamination of peanut butter.In order to reduce HCC in Sudan, pre and post harvest measures in agricultural policy need to be reinforced. At the community level, specific attention should be given to selling and processing of peanuts and their products at local markets. In addition, immunization of infants and high-risk groups against HBV infections has to be considered as a short-term strategy. Finally, future research would benefit from improved hospital and population registries