This project will continue to focus on the identification of environmental and genetic risk factors for development of hepatocellular carcinoma (HCC) in Taiwan. We are carrying out a case-control study nested in a cohort established by our collaborator, Dr. Chien in which 25,611 subjects were recruited between 1990 and 1992. In our ongoing studies, we demonstrated that, in conjunction with hepatitis B or C virus infection, aflatoxin B1 (AFB1), 4-aminobiphenyl, and polycyclic aromatic hydrocarbons (PAH) increased HCC risk. Synergistic interactions between virus and chemical were also observed. Genotyping for polymorphisms in carcinogen metabolism, oxidative stress and DNA repair are ongoing and suggest that genetic susceptibility is also significant. We will continue to analyze blood and urine samples for AFB1, and PAH biomarkers in all new cases and matched controls but also expand to biomarkers of oxidative stress including oxidized plasma proteins and urinary 8-oxodeoxyguanosine and isoprostane. We hypothesize that biomarkers of environmental exposure and oxidative stress will be higher in cases than controls. We will also continue to genotype subjects for polymorphisms in the pathways currently being investigated but expanding the number of genes. We hypothesize that cases will more frequently be carriers of """"""""higher risk"""""""" alleles than controls and that there will also be an interaction between environmental exposures and genotype. Finally, our pilot study demonstrated that p16 was frequently methylated in tumor DNA isolated from plasma of HCC cases. We will now carry out a case-control study within the cohort to determine the frequency of methylation of a panel of genes. We hypothesize that methylation will be more frequent in cases than controls. These studies will allow the development of a panel of genes in which the detection of methylation in blood DNA identifies HCC earlier than currently possible. Our collaborative study with Dr. Chen has provided much useful data on environmental and genetic risk factors for cancer development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES005116-18
Application #
7454310
Study Section
Special Emphasis Panel (ZRG1-HOP-N (02))
Program Officer
Mcallister, Kimberly A
Project Start
1990-01-01
Project End
2010-03-31
Budget Start
2008-07-01
Budget End
2010-03-31
Support Year
18
Fiscal Year
2008
Total Cost
$337,642
Indirect Cost
Name
Columbia University (N.Y.)
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Chu, Yu-Ju; Yang, Hwai-I; Wu, Hui-Chen et al. (2018) Aflatoxin B1 exposure increases the risk of hepatocellular carcinoma associated with hepatitis C virus infection or alcohol consumption. Eur J Cancer 94:37-46
Chu, Yu-Ju; Yang, Hwai-I; Wu, Hui-Chen et al. (2017) Aflatoxin B1 exposure increases the risk of cirrhosis and hepatocellular carcinoma in chronic hepatitis B virus carriers. Int J Cancer 141:711-720
Yeh, Chih-Ching; Goyal, Abhishek; Shen, Jing et al. (2017) Global Level of Plasma DNA Methylation is Associated with Overall Survival in Patients with Hepatocellular Carcinoma. Ann Surg Oncol 24:3788-3795
Zeng, Hui; Wu, Hui-Chen; Wang, Qiao et al. (2017) Telomere Length and Risk of Hepatocellular Carcinoma: A Nested Case-control Study in Taiwan Cancer Screening Program Cohort. Anticancer Res 37:637-644
Wu, Hui-Chen; Yang, Hwai-I; Wang, Qiao et al. (2017) Plasma DNA methylation marker and hepatocellular carcinoma risk prediction model for the general population. Carcinogenesis 38:1021-1028
Shen, Jing; Wang, Qiao; Gurvich, Irina et al. (2016) Evaluating normalization approaches for the better identification of aberrant microRNAs associated with hepatocellular carcinoma. Hepatoma Res 2:305-315
Wu, Hui-Chen; Shen, Jing; Yang, Hwai-I et al. (2016) Blood DNA methylation markers in prospectively identified hepatocellular carcinoma cases and controls from Taiwan. World J Hepatol 8:301-6
Shen, Jing; Siegel, Abby B; Remotti, Helen et al. (2016) Identifying microRNA panels specifically associated with hepatocellular carcinoma and its different etiologies. Hepatoma Res 2:151-162
Ruan, Peifeng; Shen, Jing; Santella, Regina M et al. (2016) NEpiC: a network-assisted algorithm for epigenetic studies using mean and variance combined signals. Nucleic Acids Res 44:e134
Shen, Jing; Yeh, Chih-Ching; Wang, Qiao et al. (2016) Plasma Adiponectin and Hepatocellular Carcinoma Survival Among Patients Without Liver Transplantation. Anticancer Res 36:5307-5314

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