Development of a Biomarker for Dietary Furanocoumarins

描述（由申请人提供）：该项目预计通过教学和研究活动，补充候选人的研究呋喃香豆素和人类癌症预防的5年目标和研究饮食模式和预防癌症的10年目标，发展候选人的职业生涯。具体而言，职业发展计划包括以下目标：1）获得生物标志物开发的知识和技能，2）培养饮食和癌症预防的流行病学研究技能，3）建立跨学科研究协会和合作。该研究计划将利用明尼苏达大学共济会癌症中心（NCI指定的综合癌症中心）的广泛资源和专业知识，以解决两个具体目标。第一个目标是开发一种饮食暴露于呋喃香豆素的尿液生物标志物，呋喃香豆素是一组化合物，可以通过抑制致癌物的活化来降低癌症风险。第二个目的是验证用于流行病学研究的生物标志物，以在癌症预防研究的这一领域产生更多的人类数据。来自共济会癌症中心的高级教师将提供科学和专业的指导，以及来自新加坡大型前瞻性队列的数据和尿液样本。首先，我们将修改现有的植物和各种人类生物标本的呋喃香豆素分析方法，并开发一种方法，用于与合并的人类尿液样品与感兴趣的分析物加标。在确定了每种分析物最佳表征的必要条件和步骤后，我们将使用来自10名给予受控量呋喃香豆素食物来源的个体的尿样对该方法进行化学验证，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）和来自新加坡华人健康研究的尿液样本，我们将使用现场尿液样本验证尿呋喃香豆素生物标志物的使用。这将包括分析来自新加坡的呋喃香豆素食物来源，以根据食物频率问卷数据计算呋喃香豆素摄入量。相关性：该项目的结果将为后续研究提供急需的工具，以确定膳食中的糠酸盐是否可以降低癌症的风险，癌症是美国第二大死亡原因。该项目还将扩大可用的饮食生物标志物的数量，以及评估各种饮食模式是否能预防癌症的能力。

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.