The long-term goal of this revised application is to design effective prevention strategies for reducing the incidence of liver cancer in high-risk populations. Primary liver cancer, mainly hepatocellular carcinoma (HCC), is one of the most common cancers in Asia and Africa. The poor prognosis of this malignancy results in it being the third most common cause of cancer deaths in the world. Chronic infection with hepatitis B viruses (HBV) and dietary aflatoxin exposure are two major etiologic risk factors for HCC in high-risk areas. The great challenge in cancer prevention and control is how to manage those who have already been exposed to carcinogens, such as individuals who are HBsAg carriers and have long-term aflatoxin exposure. Chemoprevention has been proposed as the good tool to target these high-risk populations. Among various identified chemopreventive agents, green tea polyphenols (GTP) have been shown to be safe and high effective in inhibition of carcinogen-induced mutagenesis and tumorigenesis in bioassays and animal models for different target organ sites, including aflatoxin-induced liver tumors.
The specific aims for this study are (1) to incorporate molecular biomarkers analysis for aflatoxin exposure, HBV infection, and oxidative DNA damage into an on-going randomized, double blinded, and placebo-controlled intervention trial of GTP in 1,800 residents who are double seropositive of HBsAg and aflatoxin-albumin adduct in Fusui County, Guangxi Zhuang Autonomous Region, People's Republic of China; efficacy of the chemopreventive trial will be determined by monitoring changes of levels of risk-factor specific molecular biomarkers and the actual incidence of HCC in the studied population. (2) to examine and assess the efficacy of GTP in reducing aflatoxin biomarkers by measuring aflatoxin-albumin adducts in serum and various aflatoxin biomarkers in urine collected from 300 participants in different time of the study. Difference in metabolic phenotypes/genotypes as they related to aflatoxin biomarker levels will be determined. (3) to evaluate the inhibitory effect of GTP on HBV-associated markers including HBV-DNA replication and HBV-induced immunologic changes in serum samples. (4) to determine antioxidative role of GTP in inhibition of the level of 8-hydroxy-2'-deoxyguanosine in urine samples collected from the study participants and (5) to determine and assess long-term bioavailability and biotransformation of GTP and the long-term toxicological effect of GTP on study participants. The results of this study would help to evaluate the chemoprotective effect of GTP against human HCC and to understand the molecular mechanisms of GTP in chemoprevention of human HCC caused by well-defined major risk factors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA090997-06
Application #
7759893
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Umar, Asad
Project Start
2003-06-16
Project End
2010-08-31
Budget Start
2009-07-07
Budget End
2010-08-31
Support Year
6
Fiscal Year
2007
Total Cost
$319,068
Indirect Cost
Name
University of Georgia
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
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Wang, Jincheng; Tang, Lili; Wang, Jia-Sheng (2015) Biomarkers of Dietary Polyphenols in Cancer Studies: Current Evidence and Beyond. Oxid Med Cell Longev 2015:732302
Yang, Zhendong; Xue, Kathy S; Sun, Xiulan et al. (2015) Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans. Toxins (Basel) 7:5224-35
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Qian, Guoqing; Xue, Kathy; Tang, Lili et al. (2012) Mitigation of oxidative damage by green tea polyphenols and Tai Chi exercise in postmenopausal women with osteopenia. PLoS One 7:e48090
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Shen, C-L; Yeh, J K; Cao, J J et al. (2010) Synergistic effects of green tea polyphenols and alphacalcidol on chronic inflammation-induced bone loss in female rats. Osteoporos Int 21:1841-52
Shen, Chwan-Li; Yeh, James K; Cao, Jay J et al. (2010) Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model. J Nutr Biochem 21:968-74
Xu, Li; Qian, Guoqing; Tang, Lili et al. (2010) Genetic variations of hepatitis B virus and serum aflatoxin-lysine adduct on high risk of hepatocellular carcinoma in Southern Guangxi, China. J Hepatol 53:671-6

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