Date of Award

3-21-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Applied Science

First Advisor

Nawab Ali

Abstract

Colorectal cancer is the second most leading cause of cancer related deaths in the Western countries. Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as "Lynch Syndrome", is a genetic disorder that accounts for 5-10 % of all diagnosed colorectal cancers. It is caused by genetic defects in DNA mismatch repair proteins including MLH1 and MSH2. The aim of this PhD dissertation research was to develop a sensitive and reliable diagnostic method to screen patients with this syndrome before they develop colorectal cancer. The current methods to screen HNPCC patients are expensive, time consuming and insensitive. The new method would address these issues. The hypothesis is that normal human population is predicted to have the ratio of the MLH1 and MSH2 proteins close to 1.0, the deviation from it would be considered a risk factor. Furthermore, the deficiency of these proteins may also cause resistance to certain anti-cancer drugs. As a result, these drugs will fail to treat patients with HNPCC syndrome. This issue was addressed by studying the effectiveness of anti-cancer drugs using colorectal carcinoma cell lines that differentially express MLH1 and MSH2 proteins. This research has significance in early screening, diagnosis and treatment of HNPCC.

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