RESEARCH PROJECT 1: Chemical and Viral Biomarkers of Exposure and Risk (Groopman)

在亚洲许多地区，肝细胞癌是癌症发病率和死亡率的主要原因， 包括中国和泰国，以及撒哈拉以南非洲，那里有60多万新病例 以及每年的死亡人数。确诊年龄的中位数在45岁到45岁之间，加剧了肝细胞癌的影响 50年来，它几乎总是致命的。已知的与糖尿病发病相关的主要病因 这些地区的肝细胞癌是感染了乙肝病毒(乙肝病毒)和/或丙型肝炎病毒(丙型肝炎病毒) 饮食中暴露于高水平的黄曲霉毒素B1(AFB1)。肝癌也是#年上升最快的实体肿瘤。 在美国，而且在少数族裔社区中比例过高。虽然对肝细胞癌病因学的了解刺激了 许多机制研究对本病的发病机制进行了了解，这些信息只是 开始转化为在高危人群中制定预防和临床干预措施。 该项目的目标是开发和验证反映暴露生物效应的生物标记物。 化学和病毒毒物在肝癌病因学中的作用。在包括癌症在内的所有慢性人类疾病中， 环境中暴露于多种环境因素是重要的因素。这样做的具体目的是 项目包括：1)开发尿液黄曲霉毒素代谢物的有效同位素稀释LC-MS方法： 氧化黄曲霉毒素；黄曲霉毒素硫代尿酸；咪唑环开环Fapy加合物和黄曲霉毒素-赖氨酸 加合物；2)确定乙肝病毒(乙肝病毒)突变和血清DNA中P53突变预测能力 中国和西非农村队列中的肝癌风险；以及3)扩大我们对以下人群相互作用的评估 丙型肝炎病毒、乙肝病毒和黄曲霉毒素暴露是肝细胞癌发病的危险因素 泰国北部。该项目致力于开发生物标记物的创新定量方法， 用于评估高危人群的初级和化学预防干预措施的有效性。 肝癌的人群。这些生物标志物已经并将继续使用队列研究和 然后将描述它们与疾病风险的关系。

Hepatocellular carcinoma (HCC) is a major cause of cancer morbidity and mortality in many parts of Asia, including China and Thailand, and in sub-Saharan Africa, where there are upwards of 600,000 new cases and deaths each year. The impact of HCC is exacerbated by a median age of diagnosis of between 45 and 50 years and it is nearly always fatal. The major known etiological factors associated with development of HCC in these regions are infection with hepatitis B (HBV) and/or hepatitis C (HCV) virus and lifetime exposure to high levels of aflatoxin B1 (AFB1) in the diet. HCC is also the most rapidly rising solid tumor in the US and is overrepresented in minority communities. While knowledge of the etiology of HCC has spurred many mechanistic studies to understand the pathogenesis of this disease, this information is only just beginning to be translated into development of preventive and clinical interventions in high risk populations. The goals of this project are to develop and validate biomarkers reflecting the biological effects of exposures to chemical and viral toxicants in the etiology of liver cancer. In all chronic human diseases, including cancer, ambient exposures to multiple environmental agents are significant contributors. The specific aims of this project are: 1) To develop validated isotope dilution LC-MS methods for urinary aflatoxin metabolites: oxidized aflatoxins; aflatoxin mercapturic acid; the imidazole-ring opened FAPY adduct and aflatoxin-lysine adducts; 2) To determine the power of mutations in hepatitis B virus (HBV) and p53 in serum DMA to predict HCC risk in cohorts in rural China and West Africa; and 3) To extend our assessment of interactions among hepatitis C virus (HCV), HBV and aflatoxin exposure as risk factors for HCC development in a cohort in Northern Thailand. This project is working to develop innovative quantitatitive methods for biomarkers that are applied to the assessment of the efficacy of both primary and chemoprevention interventions in high-risk populations for HCC. These biomarkers have been and will continue to be validated using cohort studies and their relation to disease risk will then be characterized.