SELENIUM AND LUNG CANCER RISK IN ASBESTOS WORKERS

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DESCRIPTION: (Applicant's Description) Lung cancer accounts for more cancer deaths in the United States than breast, prostate and colorectal cancer combined. Efforts to improve early detection, develop successful screening programs and find effective chemopreventive agents are desirable. Selenium has shown promise as a cancer chemopreventive agent in animal and human studies. A putative mechanism of selenium's anticarcinogenic activity is its integral part in cellular antioxidant systems. Asbestos-exposed workers have a well established increased incidence of lung cancer, and asbestos carcinogenesis is thought to involve activated oxygen species. In a cross-sectional study of asbestos-exposed workers, a large number of individuals were found to have moderate sputum atypia (28 percent), a marker of lung cancer risk. The major hypothesis of this proposal is that asbestos-exposed workers treated with oral selenium-rich yeast (200gg/day) will show significant improvement in intermediate end-point biomarkers of lung cancer risk compared to placebo; and furthermore, changes in markers of lung cancer will be accompanied by decreases in markers of oxidative cellular damage. The study design is a randomized, placebo-controlled, double blind trial of asbestos-exposed construction trades workers using high selenium yeast supplementation. Markers of lung cancer risk to be examined include sputum cytologic atypia, endobronchial metaplasia/dysplasia, and nuclear morphometry of sputum and endobronchial biopsy specimens. The mechanism of action of selenium will be investigated using markers of oxidative cellular damage, including 8-hydroxydeoxyguanosine (a marker of DNA damage), malondialdehyde (a marker of lipid peroxidation), and 8-iso-prostaglandine F2, (a marker of lipid peroxidation), before and after the intervention. The proposed study will assess whether selenium is effective in reversing premalignant lesions indicative of increased lung cancer risk and elucidate potential mechanisms of action of selenium. As such, this study will provide a critical foundation to further establish selenium as a potential chemopreventive agent for human lung cancer.