Hepatitis C virus (HCV) infection and alcohol abuse are the 2 major risk factors for hepatocellular carcinoma (HCC) in this country. The higher prevalence of HCV infection in the general population has resulted in a significant increase of the incidence of HCC in the United States. Although both HCV and alcohol can independently induce liver disease, exposure to both agents may accelerate the course of liver pathology and/or lead to more severe injury. The mechanism underlying the synergistic effect of HCV and alcohol intake is not well understood. One hypothesis is that both HCV and alcohol intake may contribute to chronic hepatitis, cirrhosis and subsequent liver cancer through enhanced oxidative stress. It is known that alcohol could induce oxidative stress and lipid peroxidation. Interestingly, a recent study has reported that HCV encodes a selenium (Se)-dependent antioxidant enzyme, glutathione peroxidase, GPx, and GPx may have a regulatory role in HCV replication. The virus-induced overexpression of GPx may lead to a decreased level of Se in the host due to the competition of HCV for Se. In fact, patients with HCV have been shown to have a significant decline in their serum Se. On the other hand, the hepatotoxicity of ethanol and its associated malnutrition will further reduce the cellular Se level. This additive decline in the Se level will make the cell more susceptible to reactive oxygen species (ROS). Previous studies have shown an association between oxidative DNA damage and either alcohol exposure or chronic viral infection. It seems that chronic HCV infection may lead to an increased ROS, overexpression of GPx and reduced serum level of Se. When the Se-GPx level is low, the virus will be more provoked for replication, leading to a higher viral load in the infected cell. Eighty newly-diagnosed HCC patients will be recruited from University of Texas MD Anderson Cancer Center (UTMDACC). The current project will explore the effect of dietary selenium intake and its interaction with HCV and alcohol intake in HCC in a case-control study. Eighty healthy individuals (first control group), matched with cases by age, sex and ethnicity, will be recruited from the patients non-blood relatives and friends from UTMDACC. To have a control group with comparable prevalence of HCV infection, 80 patients with liver cirrhosis, who have no evidence of HCC (second control group), will be recruited from Baylor College of Medicine. Information on alcohol intake, dietary Se intake and other risk factors will be collected by a questionnaire. The frequency and profile of hepatitis B virus (HBV) and HCV infection will be determined by measuring serum HBsAg, anti-HBC, anti-HCV, and HCV-RNA. Oxidative stress will be evaluated by measuring the levels of serum Se, GPx activity, lipid peroxides, and 8-hydroxy-deoxyguanosine (8-OH-dG), a marker of oxidative DNA damage. The expression of GPx and the level of 8-OH-dG will also be measured in tissue samples from cirrhotic and HCC patients. Serum Se, GPx activity, lipid peroxides and oxidative DNA damage will be measured in relation to HCV and alcohol intake history.
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