Green Tea and Reduction of Breast Cancer Risk

Principal Investigator: Mindy S. Kurzer, PI

Funding Source: National Institutes of Health (NIH)

Grant Period: Ongoing

Abstract: Green Tea and Reduction of Breast Cancer Risk Abstract
The ultimate goal of this proposal is to gain a full understanding of the mechanisms by which tea catechins inhibit breast carcinogenesis in humans. Green tea catechins have been shown to inhibit mammary carcinogenesis in rodents, and epidemiological studies, although inconsistent, have shown that women who regularly drink green tea have reduced breast cancer risk. This inconsistency may likely be due to genetic differences in catechin metabolism. Previous studies have shown that green tea consumption is associated with reduced breast cancer risk only in women with the low-activity catechol-O methyltransferase (COMT) genotype. This is consistent with the understanding that COMT activity significantly influences catechin metabolism and excretion. The purpose of this proposal is to perform a clinical trial to test the hypotheses (generated from experimental animal and epidemiological studies) that green tea consumption reduces breast cancer risk, and that this effect is seen primarily in women with the low-activity COMT genotype.We will study this by evaluating the effects of green tea extract on breast cancer biomarkers in women who have been recruited on the basis of their COMT genotype.We will conduct a randomized, double-blind, placebo-controlled trial in 800 postmenopausal women who are in the upper half of mammographic density, a recognized risk factor for breast cancer. The 800 high-risk women (400 low-activity and 400 high-activity COMT genotype) will receive green tea extract containing 800 mg epigallocatechin gallate (EGCG, the most potent of the tea catechins) or placebo pills daily for 12 months. Our primary aims are to determine the effects of 12 months of green tea extract supplementation on the following recognized biomarkers of breast cancer risk: mammographic density; plasma insulin-like growth factor 1 (IGF-1), IGF binding protein 3, estrone, estradiol, androstenedione and sex hormone binding globulin. Our secondary aims are to determine the effects of green tea extract on proposed biomarkers of breast cancer risk including urinary estrogen metabolites and plasma F2-isoprostanes. We hypothesize that the beneficial effects of green tea extract on these biomarkers will be seen primarily in the low-activity COMT group. By using a nutrigenomic approach, this targeted nutrition intervention study will help clarify the mechanisms by which green tea lowers breast cancer risk as well as identify a subpopulation most responsive to green tea.