EPIDEMIOLOGY OF RECTAL MUCOSAL PROLIFERATION

University Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

DESCRIPTION: Colorectal cancer develops as a consequence of abnormalities and proliferation in cell death that may be induced by environmental exposures. This ongoing project has been examining the epidemiologic aspects of colorectal cancer precursors for the past eight years. The first phase of the study examined dietary and lifestyle factors associated with colorectal adenomas. The second phase studied rectal mucosal proliferation. This proposed third phase will examine the role of programmed cell death (apoptosis) in the development of colorectal neoplasia based on the hypothesis that levels of apoptosis may be an important marker of malignant potential. Decreased apoptosis permits mutated cells to continue to proliferate, thus promoting carcinogenesis. The proposed study will measure not only apoptosis, using in-situ end-labelling (ISEL) and light microscopy, but also, proliferation, using proliferating cell nuclear antigen (PCNA) and whole crypt mitotic count (WCMC). Study subjects will be 400 consenting male and female patients who meet study eligibility criteria. Rectal mucosal pinch biopsies will be taken from subjects during routine colonoscopy and immediately processed. The Specific Aims of the study are to: 1) evaluate the association between the apoptosis/proliferation index and the presence of colon adenomas and cancers; 2) examine the association between apoptosis/rectal mucosal proliferation and specific dietary factors that have been associated with colorectal cancer; and 3) assess the association between apoptosis/rectal mucosal proliferation and specific lifestyle factors and drugs that have been associated with risk of colorectal cancer. A secondary Aim will include examination of whether selenium levels correlate with apoptosis and proliferation indices. The study is an direct extension of ongoing research. The concept of a decreased rate of apoptosis in the pathogenesis of cancer is a relatively new one that has not been previously examined in comprehensive epidemiologic studies of either colorectal cancer or its precursor.