MOLECULAR EPIDEMIOLOGY OF PRIMARY HEPATOCELLULAR CARCINOMA IN SENEGAL

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The primary goal of this project is to test the hypothesis that exposure to aflatoxin-B1 (AFB1) is etiologically associated with primary hepatocellular carcinoma (PHC). Although there is considerable circumstantial evidence to support this hypothesis, the lack of both person-specific measures of exposure and prospective follow-up of exposed individuals have prevented an adequate evaluation. The proposed study will be conducted in Senegal, west Africa, where PHC is the major cause of cancer deaths, consumption of AFB1 contaminated peanuts is very common, and hepatitis B virus (HBV) infection is endemic. Approximately 80% of PHCs in Senegal have been associated with chronic HBV infection . The study population will consist of the entire 18,000 man Senegalese Army, a group that can be followed for 5 or more years with essentially 100% ascertainment of PHCs. To maximize efficiency and cost effectiveness, a nested case-control design will be used. About 40 cases of PHC are expected to occur during the study. An assay of AFB1-albumin adducts in serum will be used to determine person-specific AFB1 exposure over time. In order to estimate an individual's average AFB1 exposure, it will be necessary to ascertain the intraindividual, seasonal, and geographic variation in AFB1 exposure. Environmental and genetic factors may influence an individual's response to AFB1. Such factors include: dietary selenium and consumption of naturally occurring chemoprotective agents in foods (green tea, cruciferous vegetables). Other factors may affect the risk of PHC including: tobacco and alcohol use and infection with hepatitis viruses C and delta (D). The Specific Aims of this project are to evaluate these factors individually and interactions of these factors in relation to risk of PHC. In the United States, the permissible aflatoxin content of commercially manufactured peanut butter (FDA action level) is 20 parts per billion. To evaluate the relevance of the federal standard, particularly to immigrant and drug using populations in the U.S. with high prevalences of HBV and HCV infections, it is necessary to do studies in locations with high levels of aflatoxin exposure, like Senegal, and to extrapolate the results to areas with lower levels of exposure, like the United States. By using the Senegal Army as the study population, we will be able to conduct the first prospective investigation in Africa of AFB1 exposure, HBV infection and other confounding variables as risk factors for PHC.