Development of a Biomarker for Dietary Furanocoumarins

膳食呋喃香豆素生物标志物的开发

• 批准号: 8127790
• 负责人: Sabrina Trudo
• 金额: $ 14.96万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-24 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8127790
• 关键词: Address; Animal Model; Apiaceae; Area; Biological; Biological Assay; Biological Markers; Botanicals; CYP1A2 gene; CYP3A4 gene; Cancer Center; Carcinogen Metabolism; Carcinogens; Carrots - dietary; Cause of Death; Characteristics; Chemopreventive Agent; Chemoprotective Agent; Chinese People; Citrus; Collaborations; Complement; Comprehensive Cancer Center; Cytochrome P-450 CYP1A1; DNA Adducts; Data; Development; Development Plans; Diet; Diet Research; Dietary Practices; Dose; Drug Metabolic Detoxication; Eating; Edible Plants; Enzymes; Epidemiologic Studies; Epidemiology; Equilibrium; Excretory function; Exposure to; Faculty; Family; Food; Frequencies; Fruit; Furanocoumarins; Goals; Health; Hour; Human; In Vitro; Individual; Intake; Interdisciplinary Study; Intervention; Investigation; Isothiocyanates; Knowledge; Malignant Neoplasms; Measurement; Mediating; Metabolic; Metabolic Biotransformation; Methodology; Methods; Minnesota; NCI-Designated Cancer Center; Pattern; Phase; Phytochemical; Plants; Prevention Research; Principal Investigator; Questionnaires; Records; Reporting; Research; Research Activity; Resources; Rutaceae; Sampling; Second Primary Cancers; Singapore; Source; Spottings; Testing; Time; United States; Universities; Urine; Vegetables; Xenobiotics; anticancer research; base; bioactive food component; cancer prevention; cancer risk; carcinogenesis; career; career development; cohort; cytochrome P-450 CYP2A6 (human); diet and cancer; feeding; fruits and vegetables; human data; interest; prospective; response; skills; tool; urinary

DESCRIPTION (provided by applicant): This project expects to develop the career of the candidate through didactic and research activities that complement the candidate's 5-year goal of studying furanocoumarins and cancer prevention in humans and 10- year goal of studying diet patterns and protection against cancer. Specifically, the career development plan includes the following objectives: 1) acquire knowledge and skills in biomarker development, 2) develop skills in epidemiologic study of diet and cancer prevention, and 3) build interdisciplinary research associations and collaborations. The research plan will utilize the extensive resources and expertise at the University of Minnesota Masonic Cancer Center, an NCI designated Comprehensive Cancer Center, to address two specific aims. The first aim is to develop a urinary biomarker of dietary exposure to furanocoumarins which are a group of compounds that may decrease cancer risk through inhibiting activation of carcinogens. The second aim is to validate the biomarker for use in epidemiologic studies to generate more human data in this area of cancer prevention research. Senior faculty from the Masonic Cancer Center will provide scientific and professional guidance in addition to the data and urine samples from a large prospective cohort in Singapore. First, we will modify existing methods for furanocoumarin analysis of plants and various human biospecimens and develop a method for use with pooled human urine samples spiked with the analytes of interest. After determination of the necessary conditions and steps for optimal characterization of each analyte, we will chemically validate the method using urine samples from 10 individuals given controlled amounts of furanocoumarin food sources and study excretion time and dose response. Lastly, using diet intake data (obtained by food frequency questionnaire) and urine samples from the Singapore Chinese Health Study, we will validate the use of the urinary furanocoumarin biomarker with spot urine samples. This will include analysis of furanocoumarin food sources from Singapore to calculate furanocoumarin intake based on the food frequency questionnaire data. RELEVANCE: The results of this project will provide a much-needed tool for subsequent study of whether dietary furancoumarins can decrease the risk of cancer, the second leading cause of death in the United States. The project will also expand the number of dietary biomarkers available and the ability to assess whether various diet patterns protect against cancer.

描述（由申请人提供）：该项目希望通过教义和研究活动来发展候选人的职业生涯，这些活动补充了候选人在人类中研究Furanocoumarins和预防癌症的5年目标以及研究饮食模式和保护癌症的10年目标。具体而言，职业发展计划包括以下目标：1）获取生物标志物发展的知识和技能，2）发展饮食和癌症预防流行病学研究的技能，以及3）建立跨学科研究协会和合作。该研究计划将利用NCI指定综合癌症中心明尼苏达大学共济会癌症中心的广泛资源和专业知识来解决两个具体目标。第一个目的是开发饮食中饮食中的尿构成生物标志物，暴露于Furanocoumarins，这是一组化合物，可以通过抑制致癌物的激活来降低癌症风险。第二个目的是验证生物标志物用于流行病学研究，以在癌症预防研究领域产生更多人类数据。共济会癌症中心的高级教职员工还将提供科学和专业的指导，除了来自新加坡大型潜在队列的数据和尿液样本外。首先，我们将修改现有的植物和各种人类生物测量分析的方法，并开发一种与均匀的人类尿液样品一起使用的方法。确定了每种分析物的最佳表征的必要条件和步骤后，我们将使用来自10个个体的尿液样本进行化学验证该方法，该方法给出了受控量的Furanocoumarin食物来源，并研究排泄时间和剂量反应。最后，使用饮食摄入数据（通过食物频率问卷获得）和新加坡中国卫生研究的尿液样本，我们将验证使用尿液中富诺康素生物标志物和点尿样品的使用。这将包括根据食品频率问卷数据来计算新加坡的富诺康林食物来源，以计算Furanocoumarin的摄入量。相关性：该项目的结果将提供急需的工具，用于随后研究饮食中的雌激素是否可以降低癌症的风险，这是美国第二大死亡原因。该项目还将扩大可用饮食生物标志物的数量，并能够评估各种饮食模式是否可以防止癌症。