Increased or abnormally regulated cell proliferation plays an important role in carcinogenesis. Bombesin like peptides are growth factors for a number of cell types, including bronchial epithelial cells. A number of studies in animal models have demonstrated that pulmonary carcinogens, including tobacco smoke, can increase the level of bombesin like peptides in the lung. Studies in humans have demonstrated elevated levels of bombesin like peptides in the lower respiratory tract of clinically normal smokers: a subset of whom display levels outside the range found in nonsmokers. Urinary levels of bombesin like peptides appear to identify individuals with elevated lower respiratory bombesin like peptides. There hypotheses will be tested: 1. Elevated levels of bombesin like peptides identify individuals at high risk for the development of lung cancer. 2. Smoking cessation and/or treatment with chemopreventive agents may lower bombesin like peptide levels along with lung cancer risk. 3. The bombesin like peptide found in smokers may be a new member of this peptide family.
Specific aims i nclude: 1. Cross sectional studies of bombesin like peptide levels in lung cancer and controls. 2. Prospective analysis of a cohort of moderate to high risk smokers. 3. Serial analysis of bombesin like peptide levels in smoking cessation and chemoprevention studies. 4. Molecular characterization of bombesin like peptides in urine and bronchoalveolar lavage.
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