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Progress in Chemistry 2013, Vol. 25 Issue (09): 1454-1461 DOI: 10.7536/PC130205 Previous Articles   Next Articles

Prevention of Liver Cancer in Qidong, China：Lessons from Aflatoxin Biomarker Studies

Patricia A. Egner1, Jin-Bing Wang2, Yuan-Rong Zhu2, Lisa P. Jacobson1, Derek Ng1, Alvaro Muñoz1, Jed W. Fahey1, Jian-Guo Chen2, Tao-Yang Chen2, Geng-Sun Qian2, John D. Groopman1, Thomas W. Kensler*1,3   

  1. 1. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;
    2. Qidong Liver Cancer Institute, Qidong 226200, China;
    3. School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
  • Received: Online: Published:
  • Contact: Thomas W. Kensler E-mail:tkensler@jhsph.edu
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Primary liver cancer has been the leading cause of cancer death in Qidong, China, with about 800 deaths annually in this region of 1.1 million residents. Epidemiological studies have highlighted the importance of infection with hepatitis B virus (HBV) and dietary exposure to hepatocarcinogenic aflatoxins as key, interactive determinants of risk in Qidong and other endemic areas. Identification of these risk factors was enabled through the development of biomarkers allowing for measures of their prevalence in case-control and other study cohorts. Vaccination against HBV began in pilot studies in the 1980s in Qidong but did not become universal for newborns until earlier this decade. Despite minimal impact on cancer mortality to date, vaccination programs are poised to blunt the development of liver diseases including cancer in this region over the next generations. Strategies for reducing aflatoxin exposure are also required, especially for those already infected with HBV. We have conducted a series of proof-of-principle clinical trials in which drugs, dietary supplements and foods have been used to alter the metabolism and elimination of aflatoxins following unavoidable exposures. Using aflatoxin biomarkers as intermediate endpoints, the efficacy of these agents (oltipraz, chlorophyllin, broccoli sprout beverages) has been demonstrated, highlighting roles for frugal approaches to chemoprevention against environmental carcinogenesis. Remarkably, recent evidence garnered from retrospective analysis of archived serum samples from the past quarter century demonstrates a 40-fold drop in aflatoxin exposure in Qidong, likely driven by changes in the primary dietary staple from maize to rice. Thus, primary prevention, evoked by changing economic and agricultural policies in the 1980s, heralds the unanticipated promise of elimination of liver cancer from this endemic region in a fore-shortened timeframe.

Key words: aflatoxin-N7-guanine, aflatoxin-albumin adduct, primary liver cancer, chemoprevention

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