Mitochondrial Genome Analysis to Detect Aggressive Behavior of Premalignant Color

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DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the United States and it is commonly diagnosed in both men and women. It was estimated that 146,940 new cases were diagnosed, and 56,730 deaths from CRC occurred in 2010. The optimal management of patients with colorectal adenomatous polyps depends on the accuracy of appropriate staging strategies because patients with similar colorectal adenocarcinoma architecture display heterogeneity in the course and outcome of the disease. While a number of treatment modalities have been developed for CRC, we still are far from finding why there are a great deal of heterogeneity show by CRC patients during the course and outcome regarding the disease racial differences. Therefore, more research is needed not only to understand the basic processes that are subverted by early stages of CRC cells to gain a proliferative advantage, also why there are a great deal of racial differences show by CRC patients during the course and outcome of the disease. The accumulation of ROS and oxidative DNA damage during the course of a lifetime may be deleterious and lead to specific mitochondrial genome alterations that may be associated in the progression of CRC. Our central hypothesis is that mtDNA gene profiling in primary tissues of colorectal adenomatous polyps will identify clinically relevant patterns of mutations and expression in histological colorectal tumor stages and subgroups of Caucasian and African-American with aggressive tumors. Specific aims are: (i) to determine and evaluate the role of mtDNA polymorphism/mutations play between African American and Caucasian patients susceptibility to the progression of CRC. (ii); to determine whether there are differences in the level of mitochondrial protein expression profiles between "early" stages of colorectal tumors and normal surrounding colorectal tissue from individual patients of African-American and Caucasian origin. This study is different from other previous studies in that a multiplatform of technologies will be performed to accurately evaluate genetic changes in epithelial colorectal adenopolyps and sub-classification of patients with similar disease, correlating the results with racial/ethnical populations. Results from this study should provide basic knowledge to the development of proper clinical tests for prediction of CRC progression in patients' clinical outcome, which is required for efficacious therapies.