Curcumin chemoprevention in familial adenomatous polyposis

家族性大肠腺瘤性息肉病（FAP）是一种常染色体显性遗传病，由APC基因的种系突变引起，其特点是在年轻人中形成数百个结直肠腺瘤性息肉。如果不进行预防性结肠切除术，几乎所有受影响的患者都会患上结直肠癌。目前，唯一有效的治疗FAP的方法是结肠切除术和终身监测肠道。我们的长期目标是为FAP患者发现有效的化学预防治疗，代表一个可能为普通肠癌腺瘤-癌序列的分子调控提供见解的模型。

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).