Familial adenomatous polyposis coli (FAP) is an autosomal dominant disorder due to germline mutation of the APC gene and characterized by the formation of hundreds of colorectal adenomatous polyps in young adults. Virtually all affected patients will develop colorectal cancer if prophylactic colectomy is not performed. Presently, the only effective therapy for FAP is colectomy and lifelong surveillance of the intestinal tract. Our long term goal is to discover effective chemopreventative therapy for patients with FAP, representing a model which may provide insights into the molecular regulation of the adenoma-carcinoma sequence in ordinary intestinal cancer. Curcumin is the major yellow pigment extracted from turmeric the powdered root of the herb Curcuma longa. Curcumin has long been used as a spice in Asia and is considered a safe food additive. Curcumin has been reported by our group to regress colorectal and ileal adenomas in 5 patients with FAP without side effects. Our hypothesis is that curcumin can decrease growth of rectal-ileal and the associated epithelial hyperproliferation in FAP patients.
Our specific aims are to: a) administer curcumin to FAP patients in a randomized, placebo-controlled, double-blinded trial and sequentially determine rectal-ileal polyp number and size by using videoendoscopy. b) Sequentially assess in flat and polypoid rectal-ileal mucosa markers of epithelial proliferation (ornithine decarboxylase, polyamines and immunohistochemistry for proliferating cell nuclear antigen), apoptosis (apoptotic index by morphologic measurement and TUNEL assay), and cyclooxygenase- 2 levels (immunohistochemistry and qRT-PCR assessment of COX-2 mRNA).

Public Health Relevance

Colorectal cancer is an important American health problem being the second leading cause of cancer death in the U.S. This project will assess in patients at high risk for colorectal malignancy the ability of curcumin, long used as a spice in Asia and considered a safe food additive, to prevent the development of the colorectal adenoma (the lesion that develops into colorectal cancer).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA134620-03
Application #
8313641
Study Section
Special Emphasis Panel (ZRG1-DIG-F (90))
Program Officer
Umar, Asad
Project Start
2010-09-01
Project End
2016-07-31
Budget Start
2012-09-14
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$212,576
Indirect Cost
$82,957
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Ballester, Veroushka; Cruz-Correa, Marcia (2014) Endoscopic surveillance of gastrointestinal premalignant lesions: current knowledge and future directions. Curr Opin Gastroenterol 30:477-83