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 have shown that women who regularly drink green tea have reduced breast cancer risk. The epidemiological data are inconsistent, however, likely due to genetic differences in catechin metabolism. In fact, we 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 do this by evaluating the effects of green tea catechins 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 either 800 mg epigallocatechin gallate (EGCG, the most potent of the tea catechins) or placebo pills daily for 12 months. The green tea catechins will be given in the form of Polyphenon E (PPE), a standardized preparation of tea catechins. Our primary aims are to determine the effects of 12 months of PPE 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 PPE on the following proposed biomarkers of breast cancer risk: urinary estrogen metabolites and plasma F2-isoprostanes. We hypothesize that the beneficial effects of PPE on these biomarkers will be seen primarily in the low-activity COMT group. This is the first randomized, double- blind, placebo-controlled trial to assess the efficacy of green tea catechins on breast cancer prevention. 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 sub-population most responsive to green tea. The development of a viable chemoprevention strategy targeting high risk women could have a significant impact on breast cancer morbidity and mortality.

Public Health Relevance

Breast cancer is a leading cause of death in Western countries and incidence is increasing in Asia. This targeted nutrition intervention study will help clarify the mechanisms by which green tea lowers breast cancer risk as well as identify a sub-population most responsive to green tea. The development of a viable non-toxic chemoprevention strategy targeting high risk women could have a significant impact on breast cancer morbidity and mortality. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA127236-01A2
Application #
7523097
Study Section
Special Emphasis Panel (ZRG1-ONC-L (03))
Program Officer
Ross, Sharon A
Project Start
2008-09-23
Project End
2013-07-31
Budget Start
2008-09-23
Budget End
2009-07-31
Support Year
1
Fiscal Year
2008
Total Cost
$795,727
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Nutrition
Type
Schools of Earth Sciences/Natur
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Webster, Allison Dostal; Finstad, Deborah A; Kurzer, Mindy S et al. (2018) Quality of life among postmenopausal women enrolled in the Minnesota Green Tea Trial. Maturitas 108:1-6
Arikawa, Andrea Y; Samavat, Hamed; Gross, Myron et al. (2017) Plasma F2-isoprostanes Are Positively Associated with Glycemic Load, but Inversely Associated with Dietary Polyunsaturated Fatty Acids and Insoluble Fiber in Postmenopausal Women. J Nutr 147:1693-1699
Dostal, A M; Arikawa, A; Espejo, L et al. (2017) Green tea extract and catechol-O-methyltransferase genotype modify the post-prandial serum insulin response in a randomised trial of overweight and obese post-menopausal women. J Hum Nutr Diet 30:166-176
Samavat, Hamed; Newman, April R; Wang, Renwei et al. (2016) Effects of green tea catechin extract on serum lipids in postmenopausal women: a randomized, placebo-controlled clinical trial. Am J Clin Nutr 104:1671-1682
Dostal, Allison M; Arikawa, Andrea; Espejo, Luis et al. (2016) Long-Term Supplementation of Green Tea Extract Does Not Modify Adiposity or Bone Mineral Density in a Randomized Trial of Overweight and Obese Postmenopausal Women. J Nutr 146:256-64
Dostal, Allison M; Samavat, Hamed; Espejo, Luis et al. (2016) Green Tea Extract and Catechol-O-Methyltransferase Genotype Modify Fasting Serum Insulin and Plasma Adiponectin Concentrations in a Randomized Controlled Trial of Overweight and Obese Postmenopausal Women. J Nutr 146:38-45
Samavat, Hamed; Kurzer, Mindy S (2015) Estrogen metabolism and breast cancer. Cancer Lett 356:231-43
Dostal, Allison M; Samavat, Hamed; Bedell, Sarah et al. (2015) The safety of green tea extract supplementation in postmenopausal women at risk for breast cancer: results of the Minnesota Green Tea Trial. Food Chem Toxicol 83:26-35
Samavat, Hamed; Dostal, Allison M; Wang, Renwei et al. (2015) The Minnesota Green Tea Trial (MGTT), a randomized controlled trial of the efficacy of green tea extract on biomarkers of breast cancer risk: study rationale, design, methods, and participant characteristics. Cancer Causes Control 26:1405-19