Development of a Biomarker for Dietary Furanocoumarins

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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.