Many laboratory studies have shown an inhibitory action of green tea or the polyphenolic fraction of green tea in animal models of lung carcinogenesis. Thus, the role of tea drinking as a potential inhibitor of carcinogenesis merits careful evaluation. In our attempt at translating the abundant pre-clinical information and epidemiological data to the human population, we are proposing a Phase IIb 3-arm randomized, placebo controlled, double blinded green tea intervention trial among former smokers with chronic obstructive pulmonary disease (COPD) and >= 40 pack-years of smoking history. This population is targeted because they have been identified as having a high prevalence of premalignant dysplasia. Subjects will be randomly assigned to consume daily for six months either a standardized green tea (GT) beverage, or a defined green tea polyphenol (GTP) extract in capsule form, or placebo preparations. The hypotheses to be tested in the proposed research are 1) high consumption of GT or GTP can protect against cellular oxidative damage and 2) high consumption of GT or GTP can modulate the expression of genes involved in proliferation and apoptosis in a population at elevated risk of lung cancer. The primary endpoints will be improvement in markers of oxidative damage in DNA, lipids, and proteins (levels of 8-OHdG, 8-epi-PGF2, MDA, di-tyrosine, and catalase and glutathione peroxidase activities). The secondary endpoints will be exploratory to assess changes in the gene expression of biomarkers of proliferation (EGFR, PCNA, JUN, FOS, Ki-67) and apoptosis (bcl-2, caspase-3) in induced sputum, in addition, we will seek to determine if there are differences in adherence between the green tea preparation groups. We believe that a program of nutritional intervention by realistic dietary modifications that are effective, safe, and acceptable should be the cornerstone of lung cancer prevention strategy.
