PROGNOSTIC & PREDICTIVE FACTORS IN OUTCOME OF PATIENTS WITH COLORECTAL CANCER:

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

There is now evidence that molecular characteristics of colorectal cancer can influence prognosis and predict response to therapy. The proposed study is motivated by the belief that better information on prognostic and predictive factors will make it possible to tailor therapy to maximize benefits and reduce cost, and by a desire to understand racial disparities in colorectal cancer mortality. The specific aims of the study are: (1) To determine which patient, treatment and molecular characteristics of colon tumors are independent predictors of prognosis. (2) To determine interactions between tumor characteristics and treatment factors and the response to therapy. (3) To determine whether racial differences in tumor characteristics are responsible for the worse 5-year survival in colorectal cancer in blacks. The proposed study will take advantage of data collected in a prospective, population-based study that will obtain exceptionally detailed information on patient characteristics, treatment, outcomes as well as tumor blocks on 1000 newly-diagnosed colorectal cancer patients (600 whites and 400 blacks) drawn at random from a diverse, mixed-race, 22 county area in North Carolina. The specific molecular characteristics will include expression of protein products of genes involved in cell cycle, cell growth, apoptosis, and cellular adhesion such as p53, k-ras, calcium binding protein S 100A4, cyclin D, IGFII, TGF-betaRII, MLH1, and MSH2. These markers will be evaluated using multitumor tissue array blocks. In addition, the study will use DNA from microdissected blocks to evaluate loss of heterogeneity (LOH) on chromosomes 2p, 5q, 17p and 18q, and will assess microsatellite instability (MSI) using BAT25, BAT26 and D17S250, D5S346, D2S123.