MOLECULAR EPIDEMIOLOGY OF PRIMARY HEPATOCELLULAR CARCINOMA IN SENEGAL

这个项目的主要目标是测试暴露的假设， 黄曲霉毒素-B1（AFB 1）与原发性 肝细胞癌（PHC）。 虽然有相当多的 支持这一假设的间接证据，缺乏两者 个人特定的暴露措施和对暴露者的前瞻性随访 个人阻碍了充分的评估。 拟定研究 将在西非塞内加尔进行，那里的原发性肝癌是主要原因 在癌症死亡中，食用AFB 1污染的花生是非常重要的。 常见的，和肝炎B病毒（HBV）感染是地方病。 约 塞内加尔80%的初级保健与慢性HBV感染有关。 研究人群将包括全部18，000名塞内加尔男性 军队，一个可以跟随5年或更长时间的群体， 100%确定PHCs。 最大限度地提高效率和成本 有效性，将使用嵌套病例对照设计。 大约40个案例 在研究期间，预计会发生PHC。 血清中AFB 1-白蛋白加合物的测定将用于确定 随着时间的推移，特定人的AFB 1暴露。 为了估计一个 个人的平均黄曲霉毒素B1暴露量，将有必要确定 AFB 1暴露的个体内、季节性和地理差异。 环境和遗传因素可能会影响个人的反应 AFB1 这些因素包括：饮食中的硒和 食品中天然存在的化学保护剂（绿色茶， 十字花科蔬菜）。 其他因素可能会影响PHC的风险 包括：吸烟和饮酒以及感染丙型肝炎病毒 delta（D）。 该项目的具体目标是评估这些 这些因素的相互作用， PHC的风险 在美国，商业上允许的黄曲霉毒素含量 生产的花生酱（FDA行动水平）是十亿分之二十。 评估联邦标准的相关性，特别是 美国的移民和吸毒人群， HBV和HCV感染，有必要在有 高水平的黄曲霉毒素暴露，如塞内加尔，并推断 结果暴露水平较低的地区，如美国。 通过使用塞内加尔军队作为研究人群，我们将能够 在非洲进行首次AFB 1暴露的前瞻性调查， HBV感染和其他混杂变量作为PHC的危险因素

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.