) The goal of this proposal is to improve understanding of diet-cancer associations, by developing a dietary assessment technique which would allow accurate reporting of previous and recent citrus (and hence d-limonene) consumption. While the Mediterranean diet is associated with lower cancer rates, food preparation techniques in the Mediterranean area include more use of citrus peel than do U.S. preparation styles, possibly resulting in higher levels of d-limonene intake. In animal models, d-limonene in the diet has resulted in tumor regression. The objectives of this project are to develop and validate a supplement to the Arizona Food Frequency Questionnaire, and to further knowledge of the interrelationship of citrus consumption, dietary d-limonene and human plasma levels of d-limonene and/or its main metabolites, perillic acid and dihydroperillic acid.
The first aim of this project is to assess levels of consumption of d-limonene by (1) assessing the limonene content of different types of foods prepared with high amounts of citrus pulp and/or peel to supplement food composition database, (2) developing and validating a dietary questionnaire to assess citrus peel, pulp, and juice consumption, which can be converted to mg d-limonene per day, (3) and applying the developed questionnaire into ongoing edipemiologic research at the Arizona Cancer Center.
The second aim i s to prepare for future clinical trials by (1) determining the acceptability of citrus as dietary supplements for cancer primary prevention trials, (2) assessing plasma levels of d-limonene and its metabolites in subjects after one month of high citrus consumption, and (3) determining whether d-limonene or its metabolites can serve as a biomarker for compliance with dietary citrus peel consumption intervention. This proposal for research will be the major component of a 5 year Academic Investigator Award in which cancer prevention and epidemiology will be the focus. These studies along with continued course work in advanced epidemiology and biostatistics, and experience in teaching will provide the experience and expertise needed to function as a successful, independent cancer investigator in the future.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Academic/Teacher Award (ATA) (K07)
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Subcommittee G - Education (NCI)
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Gorelic, Lester S
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University of Arizona
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United States
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Hakim, Iman A; Hartz, Vern; Graver, Ellen et al. (2002) Development of a questionnaire and a database for assessing dietary d-limonene intake. Public Health Nutr 5:939-45
Chow, H-H Sherry; Salazar, Dawn; Hakim, Iman A (2002) Pharmacokinetics of perillic acid in humans after a single dose administration of a citrus preparation rich in d-limonene content. Cancer Epidemiol Biomarkers Prev 11:1472-6
Hakim, I A; Harris, R B (2001) Joint effects of citrus peel use and black tea intake on the risk of squamous cell carcinoma of the skin. BMC Dermatol 1:3
Hakim, I A; Harris, R B; Ritenbaugh, C (2000) Citrus peel use is associated with reduced risk of squamous cell carcinoma of the skin. Nutr Cancer 37:161-8