Abstract PL02-01: Global disparities and prevention strategies in liver cancer

Abstract

Abstract Hepatocellular carcinoma (HCC) is a major cause of cancer morbidity and mortality in many parts of the world, including Asia and sub-Saharan Africa, where there are upwards of 1,000,000 new cases each year and over 370,000 deaths annually in the People's Republic of China (P.R.C.) alone. The major etiological factors associated with development of HCC in these regions are infection with hepatitis B (HBV) and/or hepatitis C (HCV) virus and lifetime exposure to high levels of aflatoxin B1 (AFB1) in the diet. Detailed knowledge of the etiology of HCC has spurred many mechanistic studies to understand the pathogenesis of this often fatal disease and this knowledge is critical for translation to preventive interventions in high risk populations. HBV is a significant risk factor for HCC in the economically developing world where there are over 500 million viral carriers. The contribution of HBV to the pathogenesis of liver cancer is multifactorial and is further complicated by the identification of mutant variants in HBV that alter the carcinogenic process. The HBV genome encodes its essential genes with overlapping open-reading frames; therefore, a mutation in the HBV genome can alter the expression of multiple proteins. In many cases of HCC in Asia and Africa, a double mutation in the HBV genome, an adenine to thymine transversion at nucleotide 1762 and a guanine to adenine transition at nucleotide 1764 (1762T/1764A), has been found in tumors. The molecular basis for the formation of these nucleotide changes and their temporal appearance during the course of HBV infection is unclear. Thus, whether these mutational changes can be acquired and transmitted from person to person is unknown. Nonetheless, this segment of the HBV genome contains an overlapping sequence for the base core promoter and the HBV X gene; therefore, the double mutation in codon 130 and 131 of the HBV X protein reported in human HCC corresponds to the 1762 and 1764 nucleotide changes. Thus, the linkage of this alteration with disease outcomes makes it a candidate biomarker for the early detection of HCC risk in individuals. Financial support for this work was provided by the National Institute of Environmental Health Sciences through Grants P01 ES006052 and P30 ES003819. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL02-01.