Development of a Biomarker for Dietary Furanocoumarins

描述(由申请者提供)：这个项目期望通过教学和研究活动发展候选人的职业生涯，这些活动补充了候选人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癌症预防的10年目标。具体地说，职业发展计划包括以下目标：1)获得生物标记物开发方面的知识和技能；2)发展饮食和癌症预防方面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的广泛资源和专业知识，该中心是NCI指定的综合癌症中心，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记物，呋喃香豆素是一组化合物，可以通过抑制致癌物的激活来降低癌症风险。第二个目标是验证用于流行病学研究的生物标记物，以在这一癌症预防研究领域产生更多的人类数据。共济会癌症中心的资深教员将提供科学和专业指导，此外还将提供来自新加坡一大批潜在队列的数据和尿样。首先，我们将修改现有的植物和各种人类生物样本的呋喃香豆素分析方法，并开发一种用于混合添加感兴趣分析物的人类尿样的方法。在确定了每个分析物的最佳表征的必要条件和步骤后，我们将使用10个人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，利用饮食摄入量数据(通过食物频率问卷获得)和新加坡华人健康研究的尿样，我们将以现场尿样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的摄入量。相关性：该项目的结果将为后续研究提供急需的工具，以研究饮食中的呋喃香豆素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记物的数量，以及评估各种饮食模式是否可以预防癌症的能力。

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.