Molecular biomarkers for aflatoxins: From adducts to gene mutations to human liver cancer

Over the past 30 years there have been extensive efforts to investigate the association between aflatoxin exposure and human liver cancer. These studies have been hindered by the lack of adequate dosimetry data on aflatoxin intake, excretion, and metabolism in people, as well as by the general poor quality of worldwide cancer morbidity and mortality statistics. These realities have spurred the efforts to develop new technologies to assess exposure status and risk for aflatoxins, and these agents are among the few environmental carcinogens for which quantitative risk assessments have been attempted. One of the goals of these risk assessments has been the development of primary and secondary preventive intervention methods to lower the human health impact from aflatoxin exposures. The long-term goal of the research described herein is the application of biomarkers to the development of preventive interventions for use in human populations at high risk for cancer. Several of the aflatoxin-specific biomarkers have been validated in epidemiologic studies and are now available for use as intermediate biomarkers in prevention trials. The development of these aflatoxin biomarkers has been based upon the knowledge of the biochemistry and toxicology of aflatoxins gleaned from both experimental and human studies. These biomarkers have been utilized subsequently in experimental models to provide data on the modulation of the markers under different simations of disease risk. This systematic approach provides encouragement for preventive interventions and should serve as a template for the development and validation of other chemical-specific biomarkers and their application to cancer or other chronic diseases.