Biological Markers of Aflatoxin Exposure

黄曲霉毒素暴露的生物标志物

基本信息

批准号：
7250917
负责人：
Regina M Santella
金额：
$ 34.47万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-01-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7250917
关键词：
4-biphenylamine Address Aflatoxin B Aflatoxin B1 Aflatoxins Air Albumins Alcohols Alleles Aromatic Hydrocarbons Aromatic Polycyclic Hydrocarbons Base Excision Repairs Biological Assay Biological Markers Blood Blood specimen Carcinogen Metabolism Carcinogens Carcinoma Case-Control Studies Chemicals CpG Islands DNA DNA Repair DNA Repair Gene Data Deoxyguanosine Detection Development Diagnosis Diet Doctor of Philosophy E-Cadherin Early Diagnosis Environmental Exposure Exposure to Frequencies GSTM1 gene GSTP1 gene Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genotype Glutathione S-Transferase Goals Grant Hepatitis B Hepatitis B Virus Hepatitis C Isoprostanes Liver MGMT gene Malignant Neoplasms Manganese Superoxide Dismutase Metabolism Methylation Molds Mutation NAD(P)H dehydrogenase (quinone) 1, human NQO1 gene Nested Case-Control Study Nitric Oxide Synthase Nucleotide Excision Repair Numbers OGG1 gene Oxidative Stress Pathway interactions Peroxidase Pilot Projects Plasma Plasma Proteins Polycyclic Hydrocarbons Primary carcinoma of the liver cells Promoter Regions Reactive Oxygen Species Recruitment Activity Risk Risk Factors Role Sampling Screening for cancer TP53 gene Taiwan Time Tissues Tumor Tissue University Hospitals Urine Variant Viral Virus Virus Diseases XRCC3 gene adduct carcinogenesis case control catalase cigarette smoking cohort environmental agent gene environment interaction genetic risk factor glutathione S-transferase M1 glutathione S-transferase pi glutathione peroxidase GPX1 prevent programs promoter tumor urinary

项目摘要

DESCRIPTION (provided by applicant): This project will continue to focus on the identification of environmental and genetic risk factors for development of hepatocellular carcinoma (HCC) in Taiwan. We are carrying out a case-control study nested in a cohort established by our collaborator, Dr. Chien in which 25,611 subjects were recruited between 1990 and 1992. In our ongoing studies, we demonstrated that, in conjunction with hepatitis B or C virus infection, aflatoxin B1 (AFB1), 4-aminobiphenyl, and polycyclic aromatic hydrocarbons (PAH) increased HCC risk. Synergistic interactions between virus and chemical were also observed. Genotyping for polymorphisms in carcinogen metabolism, oxidative stress and DNA repair are ongoing and suggest that genetic susceptibility is also significant. We will continue to analyze blood and urine samples for AFB1, and PAH biomarkers in all new cases and matched controls but also expand to biomarkers of oxidative stress including oxidized plasma proteins and urinary 8-oxodeoxyguanosine and isoprostane. We hypothesize that biomarkers of environmental exposure and oxidative stress will be higher in cases than controls. We will also continue to genotype subjects for polymorphisms in the pathways currently being investigated but expanding the number of genes. We hypothesize that cases will more frequently be carriers of "higher risk" alleles than controls and that there will also be an interaction between environmental exposures and genotype. Finally, our pilot study demonstrated that p16 was frequently methylated in tumor DNA isolated from plasma of HCC cases. We will now carry out a case-control study within the cohort to determine the frequency of methylation of a panel of genes. We hypothesize that methylation will be more frequent in cases than controls. These studies will allow the development of a panel of genes in which the detection of methylation in blood DNA identifies HCC earlier than currently possible. Our collaborative study with Dr. Chen has provided much useful data on environmental and genetic risk factors for cancer development.

描述（由申请人提供）：该项目将继续专注于识别台湾肝细胞癌（HCC）发展的环境和遗传风险因素。我们正在开展一项病例对照研究，该研究由我们的合作者 Chien 博士建立了一个队列，该队列在 1990 年至 1992 年间招募了 25,611 名受试者。在我们正在进行的研究中，我们证明，与乙型或丙型肝炎病毒感染相关、黄曲霉毒素 B1 (AFB1)、4-氨基联苯和多环芳烃 (PAH) 会增加 HCC 风险。还观察到病毒和化学物质之间的协同相互作用。致癌物代谢、氧化应激和 DNA 修复多态性的基因分型正在进行中，表明遗传易感性也很重要。我们将继续分析所有新病例和匹配对照中的血液和尿液样本中的 AFB1 和 PAH 生物标志物，同时还将分析氧化应激的生物标志物，包括氧化血浆蛋白以及尿 8-氧化脱氧鸟苷和异前列烷。我们假设病例中环境暴露和氧化应激的生物标志物会高于对照组。我们还将继续对目前正在研究的途径中的多态性进行基因分型，但会扩大基因的数量。我们假设病例比对照更频繁地是“高风险”等位基因的携带者，并且环境暴露和基因型之间也存在相互作用。最后，我们的初步研究表明，从 HCC 病例血浆中分离出的肿瘤 DNA 中，p16 经常被甲基化。我们现在将在队列中进行病例对照研究，以确定一组基因的甲基化频率。我们假设甲基化在病例中比对照组更频繁。这些研究将允许开发一组基因，通过检测血液 DNA 中的甲基化，可以比目前更早地识别出 HCC。我们与陈博士的合作研究提供了许多关于癌症发展的环境和遗传风险因素的有用数据。