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Title: Studies in sporadic and familial colorectal adenomatous polyps
Author: West , Nicholas J.
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2013
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Evidence exists to suggest that diets high in omega-3 fatty acids may be protective against the development of colorectal cancer with in vitro and pre-clinical models. Additionally, patients with a sporadic or genetic (eg familial adenomatous polyposis (FAP)) predisposition to developing colorectal adenomatous polyps exhibit altered cell kinetics in their colorectal mucosa as compared to normal subjects. The mam body of this thesis encompasses two clinical, randomised, placebo controlled trials. The first, EPA/POL/02 assessed whether subjects with a history of sporadic colorectal adenomata had any beneficial modulation of their colorectal mucosal cytokinetics following six months treatment of eicosapentaenoic acid (EPA) in free-fatty acid form (EPA-FFA), at doses of 19/day or 2g/day, when compared to placebo. One hundred and fifty two subjects were randomised in a 1: 1: 1 ratio. At 6 months, cell proliferation was significantly reduced in the 2g/d group. There were no significant changes in apoptosis scores across the groups. There were also marked increases in the omega-3 fatty acid profiles in this group. The second study, EPA/POL/03 assessed whether 6 months treatment with 2g/day of EPA-FFA exhibited chemopreventative activity in subjects with familial adenomatous polyposis (FAP) compared to placebo. Fifty five patients with F AP and an intact rectal remnant were randomised to treatment (n=28) or placebo (n=27). Treatment was assessed by changes in number and size of polyps within an assessable area of the rectum, together with global rectal burden, as measured by video endoscopy records. Treatment with 2g/day for 6 months was associated with a significant reduction in number, size and overall rectal polyp burden. Mucosal levels of EPA were increased in the treatment arm which was safe and well tolerated. EPA-FF A therefore holds promise as a chemopreventative agent against colorectal cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available