Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. An estimated 146,940 new cases of CRC will develop in 2004, resulting in 56,730 deaths. Screening methods that detect the early development of CRC, and are thought to reduce CRC mortality by as much as 33 percent, are the goal. Despite these figures, wide spread use of screening remains poor. Consequently, alternative methods to screening that prevent the development of adenomatous polyps and their development to CRC is indicated. Ginger, which has been studied in animal and human models for its chemopreventive potential, shows promise as an agent for preventing CRC. Currently, ginger's chemopreventive mechanisms of action are unknown but are thought to be via inhibition of arachidonate pathways and other mechanisms of cellular proliferative control. However, the bioavailability of ginger as well as the optimal dose and schedule for administering ginger to effect biomarkers of inflammation has not been examined. Also, due to ginger's unique aroma, adequate blinding needs to be examined. Hence, a series of studies using a standardized (5% {6 }-gingerols) ginger product are proposed to explore these questions: (1) a Phase IA study to evaluate the single-dose pharmacokinetics, acute toxicity, and maximum tolerated dose (MTD) of ginger; (2) a study to examine the methods for effectively blinding study participants to ginger's aroma; (3) a Phase IB study to determine the multi-dose pharmacokinetics, chronic toxicity, and effect of ginger on rectal mucosa PGE2; and (4) a Phase IIA randomized, double-blinded, placebo-controlled, clinical trial, to assess the effect of ginger on PGE2 and COX2 levels in colonic mucosa and adenomas in individuals at high risk for developing polyps or CRC. This grant also proposes to train a junior researcher in the essential skills to become an independent investigator in the area of botanicals for cancer chemoprevention. This program of study is designed to develop competencies in: (1) understanding the underlying principles of chemoprevention and the development of chemopreventitive agents; (2) measuring plant metabolites in biological fluids; (3) conducting bioassays to detect inflammatory biomarkers in colonic mucosal tissue; (4) designing pre-clinical and clinical trials in the area of chemoprevention; and (5) identifying polyps and colorectal cancer when seen during colonoscopies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
1K07CA102592-01A2
Application #
6869360
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2005-08-02
Project End
2010-07-31
Budget Start
2005-08-02
Budget End
2006-07-31
Support Year
1
Fiscal Year
2005
Total Cost
$124,445
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Family Medicine
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Citronberg, Jessica; Bostick, Roberd; Ahearn, Thomas et al. (2013) Effects of ginger supplementation on cell-cycle biomarkers in the normal-appearing colonic mucosa of patients at increased risk for colorectal cancer: results from a pilot, randomized, and controlled trial. Cancer Prev Res (Phila) 6:271-81
Jiang, Yan; Turgeon, Danielle K; Wright, Benjamin D et al. (2013) Effect of ginger root on cyclooxygenase-1 and 15-hydroxyprostaglandin dehydrogenase expression in colonic mucosa of humans at normal and increased risk for colorectal cancer. Eur J Cancer Prev 22:455-60
Zick, Suzanna M; Turgeon, D Kim; Vareed, Shaiju K et al. (2011) Phase II study of the effects of ginger root extract on eicosanoids in colon mucosa in people at normal risk for colorectal cancer. Cancer Prev Res (Phila) 4:1929-37
Yu, Yanke; Zick, Suzanna; Li, Xiaoqin et al. (2011) Examination of the pharmacokinetics of active ingredients of ginger in humans. AAPS J 13:417-26
Zick, Suzanna M; Ruffin, Mack T; Djuric, Zora et al. (2010) Quantitation of 6-, 8- and 10-Gingerols and 6-Shogaol in Human Plasma by High-Performance Liquid Chromatography with Electrochemical Detection. Int J Biomed Sci 6:233-240
Zick, Suzanna M; Ruffin, Mack T; Lee, Julia et al. (2009) Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting. Support Care Cancer 17:563-72
Zick, Suzanna M; Schwabl, Herbert; Flower, Andrew et al. (2009) Unique aspects of herbal whole system research. Explore (NY) 5:97-103
Zick, Suzanna M; Djuric, Zora; Ruffin, Mack T et al. (2008) Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev 17:1930-6