MOLECULAR EPIDEMIOLOGY OF PRIMARY HEPATOCELLULAR CARCINOMA IN SENEGAL

这个项目的主要目标是测试暴露于 黄曲霉毒素-B1(AFB1)与原发性 肝细胞癌(PHC)。尽管有相当多的 支持这一假说的间接证据，两者都缺乏 暴露于个人的措施和受暴露者的预期随访 个人阻碍了充分的评估。建议进行的研究 将在西非的塞内加尔进行，那里的PHC是主要原因 在癌症死亡中，被AFB1污染的花生的消费量非常高 乙肝病毒(乙肝)感染是地方性的。大致 塞内加尔80%的PHC与慢性乙肝病毒感染有关。 研究人群将包括全部18,000名塞内加尔人 军队，一个可以被跟踪5年或更长时间的团体，基本上 PHCS的100%确定。实现效率和成本最大化 为提高疗效，将采用嵌套病例对照设计。大约40例 预计在研究期间将发生PHC。 将使用血清中AFB1-白蛋白加合物的测定来确定 随着时间的推移，特定于个人的AFB1暴露。为了估计一个 个人的平均黄曲霉毒素B_1的暴露量，需要确定 AFB1暴露的个体内、季节和地理差异。 环境和遗传因素可能会影响个体的反应 致AFB1。这些因素包括：饮食中的硒和摄入量 食品中天然存在的化学保护剂(绿茶、 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 和Delta(D)。该项目的具体目标是评估这些 各个因素以及这些因素之间的相互作用 患原发性肝癌的风险。 在美国，商业上允许的黄曲霉毒素含量 人造花生酱(FDA的行动级别)是十亿分之二十。 评估联邦标准的相关性，特别是 移民和吸毒者在美国有很高的发病率 乙肝病毒和丙型肝炎病毒感染，有必要在有 高水平的黄曲霉毒素暴露，如塞内加尔，并推断 结果被转移到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 在非洲进行第一次接触黄曲霉毒素1的前瞻性调查， 乙肝病毒感染和其他混杂变量是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.