Abstract SY27-01: The changing etiology of liver cancer
Authors: John D. Groopman
Journal: Cancer Research (2019)

Abstract Collectively liver cancer accounts for nearly 9% of all reported cancer deaths and is one of the most common causes of cancer mortality worldwide http://gco.iarc.fr/ (1). The incidence of liver cancer varies enormously globally and unfortunately the burden of this nearly always fatal disease is much greater in the less economically developed countries of Asia and sub-Saharan Africa (2). HCC is also the most rapidly rising solid tumor in the US and Central America and is overrepresented in minority communities, including African-Americans, Hispanic/Latino-Americans and Asian-Americans (1,3,4). Overall, there are more than 850,000 new cases each year and more than 300,000 deaths annually in the People’s Republic of China (P.R.C.) alone (2). In contrast with most common cancers in the economically developed world where over 90% of cases are diagnosed after the age of 45, in high-risk regions for liver cancer onset begins to occur in both men and women by 20 years of age and peaks between 40-49 years of age in men and between 50-59 years of age in women (5-7). Gender differences in liver cancer incidence have also been well described and worldwide the number of cases among men were 554,000 and 228,000 among women in 2012 (8)(9). To date, the significant etiological factors associated with development of HCC have been defined by biomarker studies and they are infection in early life with hepatitis B virus (HBV) and lifetime exposure to high levels of aflatoxin B1 (AFB1) in the diet (10,11). Over the past 25 years, an appreciation for the role of the hepatitis C virus (HCV) has also emerged. HCV is contributing to HCC being the most rapidly rising solid tumor in the US and Japan (12). Detailed knowledge of the etiology of HCC has spurred many mechanistic studies to understand the pathogenesis of this nearly always-fatal disease (10,13,14). Fortunately, the successful development and deployment of some highly effective new drugs that cure HCV infection is a major advance and will hopefully diminish the role of this virus in liver cancer (15,16). Alcohol is a recognized human carcinogen and alcoholic cirrhosis and heavy alcohol use have been repeatedly associated with an increase in HCC risk (23). However, it is unclear if alcohol use in the absence of cirrhosis influences HCC development (24). Several studies have demonstrated an increased risk of HCC up to 5-fold with consumption of more than 80g of alcohol per day or approximately 6-7 drinks per day (23). The risk of HCC ranges from borderline significant to doubled with chronic alcohol consumption of less than 80g/day (23). A synergism between alcohol and HBV and HCV infections has also been described (23,25). In economically developed countries the dramatic rise in overweight and nonalcoholic fatty liver disease has also been related to increased HCC (26-28). Of major concern for the future are the role that obesity, diabetes and general underlying fatty liver disease will play in the development of liver cancer (29-31). Both therapeutic and pre-disease interventions will need to be deployed now to blunt the impact of these risk factors in the decades to come. Collectively, the development and validation of a new generation of biomarkers reflecting complex processes such as inflammation will need to be deployed. References 1. Ferlay, J., et al. (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer., 136, E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9. 2. (2014) World Cancer Report 2014. International Agency for Research on Cancer. 3. (2005) American Cancer Society Cancer Facts and Figures 2005. 22-27. 4. El-Serag, H.B., et al. 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(2015) Hepatocellular Carcinoma and Lifestyles. J Hepatol, 028. 31. McGlynn, K.A., et al. (2015) Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis., 19, 223-38. doi: 10.1016/j.cld.2015.01.001. Epub 2015 Feb 26. Citation Format: John D. Groopman. The changing etiology of liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY27-01.