Abstract SY14-04: Global burden of liver cancer: Emerging needs in Asia.
Authors: Groopman John D. , Kensler Thomas W. 
Published: August 2014

Abstract
Globally, driven by increased life expectancy, the overall incidence of cancer is expected to nearly double over the next 20 years. Nonetheless, the target organs where these diagnoses will occur will still vary widely from country to country because of divergent exposures and other etiologic factors (1). One cancer that currently illustrates this geographic disparity is primary liver cancer (PLC). Currently, PLC is the third leading cause of cancer mortality worldwide with an estimated 696,000 deaths in 2008. Half of these PLC deaths of those deaths occur in the People's Republic of China. The major etiological factors associated with PLC in China, as established from prospective cohort studies, are chronic infection with hepatitis B virus (HBV) and extended exposure to high levels of aflatoxin in the diet, especially from corn and groundnuts (2). The largest study, comprising more than 18,000 men residing in Shanghai in the 1980s, examined HBV infection and aflatoxin exposure as independent and interactive risk factors for PLC (3). This nested case control study revealed a statistically significant increase in the relative risk (RR) of 7.3 for men who were chronically infected with HBV (HBsAg) but unexposed to aflatoxin. In men on whom urinary aflatoxin but not HBV biomarkers were detected, the RR was 3 (4). Furthermore, in men exhibiting both urinary aflatoxin biomarkers and positive HBsAg status, the RR was 59.4.3 A subsequent cohort study in Taiwan confirmed these results.4 In light of this synergistic interaction, programs to eliminate either factor, or both, should have substantial impact on the burden of PLC.
Chronic infection with HBV has been long regarded as the major cause of PLC and initiatives have been undertaken to implement universal immunization programs. It is estimated that more than 90% of countries now routinely vaccinate newborns against HBV, and approximately 70% are now delivering 3 immunization doses. Newborns are targeted because HBV transmission is often vertical from mother to child at birth or during the perinatal period. In 1986, Taiwan became the first region to vaccinate all newborns against HBV. Since then, the number of HBV carriers in the juvenile population has declined dramatically. As of 2009, incidence of hepatocellular carcinoma was significantly lower among children aged 6-19 years in vaccinated compared with antecedent unvaccinated birth cohorts (5).
For many years, we have been working with colleagues in Qidong, China, located at the mouth of the Yangtze River, an endemic area for liver cancer, where early age of onset and high mortality rates from PLC are reported (6). HBV vaccination of newborns in the rural townships was initiated during the 1980s but did not become universal until 2002. Crude rates of PLC per 100,000 residents of Qidong rose slightly from 1972 through 1990 at levels around 50/100,000 before increasing in the 1990s to a stable rate of about 75/100,000. Such data have led to the perception that Qidong remains an irrevocably high-risk region (7). However, the latter PLC mortality rate increase largely reflects a dramatically altered age distribution in the population rising from 17.0% over 50 years of age in 1973 to 22.7% in 1988 and 34.2% in 2003. Prognosis for survival from liver cancer following diagnosis remains poor: currently &lt;10% of patients survive 1 year after diagnosis in Qidong (8). While there have been no significant changes in rates of mortality from PLC over age 40 over the past half century, there has been a 60-75% decline seen in people born after 1973. Given the timeline of HBV vaccination, it is unlikely that this program has had much impact on PLC mortality in this region as yet.
In order to accurately describe aflatoxin exposures over the past quarter century, frozen serum samples collected since 1989 were measured for aflatoxin-albumin adduct content (9–11). There has been a dramatic decline in levels of exposure from the 1980s to the present. Median levels of aflatoxin-albumin adducts from residents of the villages of Daxin and HeZuo declined from 19.3 pg/mg albumin in 1989, to 3.6 in 1995, to 2.3 in 1999, to 1.4 in 2003 and undetectable (i.e., &lt;0.5 pg/mg) in 2009 (median estimated at 0.2) and 2012 (median estimated at 0.06). Only 23% and 7% of serum samples had levels above 0.5 pg/mg of this internal dose biomarker in 2009 and 2012, respectively. These data strongly track with PLC reduction in the younger birth cohorts and points to the need for closer attention to the roles of environmental factors such as aflatoxins is warranted as a range of public health strategies are developed and implemented for the prevention of PLC in high-risk populations (12).
Acknowledgments
This work has been funded by the National Institutes of Health USA (P01 ES 006052) and the National Science and Technology Mega-Projects of China (No. 2008ZX10002-015, No. 2012ZX10002-008.
Citation Format: John D. Groopman, Thomas W. Kensler. Global burden of liver cancer: Emerging needs in Asia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY14-04. doi:10.1158/1538-7445.AM2013-SY14-04