Curcumin for the Chemoprevention of Colorectal Cancer

Specific Aims:

* To determine if curcuminoids modulate cellular proliferation as measured by proliferating cell nuclear antigen (PCNA) in the colorectal mucosa of subjects with previously resected adenomatous colonic polyps.

Hypothesis: Curcuminoids decrease cellular proliferation in the colorectal mucosa of subjects with previously resected sporadic adenomatous colonic polyps.

* To determine if curcuminoids modulate apoptosis, as measured by TUNEL assay, in the colorectal mucosa of subjects with previously resected adenomatous colonic polyps.

Hypothesis: Curcuminoids increase apoptosis in colorectal mucosa of subjects with previously resected sporadic adenomatous colonic polyps.

* To determine if curcuminoids modulate COX-2 expression as measured by immunohistochemical assays in subjects with previously resected adenomatous colonic polyps

Hypothesis: Curcuminoids decrease colorectal mucosa COX-2 expression in subjects with previously resected sporadic adenomatous colonic polyps.

* To determine if curcuminoids modulate COX-2 activity as measured by urinary eicosanoids

Hypothesis: Curcuminoids decrease concentrations of urinary eicosanoids.


Eligibility Criteria:
Inclusion Criteria:

* Age\>18
* A diagnosis for colon/rectal polyp resection, polypectomy
* Subjects must be able to have the capacity and must be willing to provide informed consent
* Premenopausal women must be surgically incapable of childbearing or be using a medically acceptable method of contraception (oral contraceptives, diaphragms, condoms with spermicide, IUD, progesterone injection or implant) throughout the entire length of the study
* Men should wear condoms during the duration of the study given the unknown effects of curcumin on sperm viability, fertility

Exclusion Criteria:

* Previous or current history of colorectal cancer
* Previous history of Familial Polyposis Syndromes
* Previous history of inflammatory bowel disease
* Previous surgery of the large bowel
* Liver disease defined as AST and ALT\>3x upper limit of normal
* Known history of gallstones, biliary colic or serum bilirubin \>2.0
* Cardiac disease including myocardial infarction, congestive heart failure, arrhythmia
* Renal disease defined as creatinine \>1.5
* Hematopoietic disease defined as WBC\<4000, platelet count \<100,000, hemoglobin\<10.0 or coagulation or bleeding disorder
* Significantly impaired gastrointestinal function or absorption
* Peptic ulcer disease
* Active infection including viral, bacterial, atypical or fungal infections of any organ system including HIV
* Previous history of allergy to turmeric, Indian curries, aspirin or NSAIDs
* Pregnant or lactating women
* Dementia or other neurologic or psychiatric disease which may impede the ability to follow the protocol
* Inability to swallow pills
* Prior or concurrent therapy with any herbal or dietary supplement containing curcuminoids
* Concurrent use of anticoagulants or antiplatelets including warfarin, clopidogrel
* Prior or concurrent use of colorectal cancer chemopreventive agents including herbals: Sulindac or other NSAIDs, aspirin, COX-2 inhibitors, 5-aminosalicylate, folate, calcium, or their use within 14 days of enrollment
* Concurrent use of immunosuppressants