There is substantial epidemiologic and experimental evidence of a protective effect of a high intake of vegetables and fruits against lung cancer in smokers, nonsmokers, and passive smokers. It is probable that b-carotene, a-tocopherol, and other antioxidants are responsible for at least part of the protective effect, but how much of it they account for is uncertain. The results of chemopreventive trials that used these nutrients or their synthetic analogues have not yet confirmed protective effects against lung cancer. Although the diets and blood levels of smokers are known generally to be lower in antioxidant nutrients and folic acid than those of nonsmokers, only a few investigators have measured the levels of these micronutrients in respiratory tissues. It is in these tissues where the potential for cigarette smoke to oxidize and destroy micronutrients should be most pronounced.
The specific aims of the proposed (NIH) studies are to determine: 1) whether the reduced blood levels and dietary intakes of micronutrients known to occur in smokers are associated with corresponding reductions in their levels in alveolar epithelial lining fluid (ELF); 2) whether reduced vitamin levels in ELF are associated with increased levels of surrogate intermediate endpoint biomarkers in the bronchial mucosa; ad 3) what the effects of smoking cessation and vitamin supplementation are on micronutrient levels in blood, ELF, and alveolar macrophages, and on the occurrence of biomarkers, in smokers and nonsmokers. The levels of b-carotene, vitamins A, C, E, B12, folic acid, and homocysteine will be measured in the blood, ELF, alveolar macrophages, and diets of 140 smokers and 40 nonsmokers; the expression of a number of biomarkers will be measured in bronchial biopsies. For smokers, these measurements will be repeated 7 days, and again 2 months, after smoking cessation intervention. Following this, US RDA-level supplements of the micronutrients will be administered, and the evaluations repeated again after 2 months. nonsmokers, after baseline evaluation, will directly enter a 2-month vitamin supplementation period, following which the evaluations will be repeated. The investigators applied to the National Cancer Institute in June, 1994 for funding to conduct these studies, but a grant was not awarded, primarily because of insufficient preliminary data. Under GCRC support, we propose to study 13 smokers and 3 nonsmokers in an abbreviated protocol, in order to document the feasibility of recruiting subjects, and to gather preliminary data. We will use simultaneous smoking cessation (for smokers) and vitamin supplementation (for both smokers and nonsmokers) for 2 months as the interventions, in order to magnify the desired changes. We will perform the assays of vitamin levels in blood and ELF, and biomarkers, as described above. Once these data are analyzed, we will calculate the larger study's power more precisely, and reapply to the National Cancer Institute.
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