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Biomarkers can be used to measure the presence of a wide variety of parent compounds and metabolites in body fluids and excreta, and serve as biomarkers of internal dose. Chemical-macromolecular adducts formed in blood and tissue or excreted in urine serve as biomarkers of exposure as well, and in many instances reflect both exposure and additional relevant biological processes. An assortment of analytical techniques have been developed to identify and measure parent compounds, metabolites, chemical-DNA and protein adducts. This chapter will discuss many analytical techniques that measure biomarkers in molecular epidemiologic studies, including biological, physical, chemical and immunological methods.

Clinical cancer prevention trials that use disease as the end-point are of necessity large, lengthy and costly. While such trials will always remain the 'gold standard' for establishing efficacy, they are unwieldy and inefficient for the rapid translation of our accelerating understanding of the molecular basis of cancer into preventive strategies. The inclusion of biomarkers in the process of chemopreventive agent development is crucial for the advancement of the field. This overview highlights the types of approach that are being used in the development and application of biomarkers in chemoprevention studies. Biomarkers, which measure exposure, susceptibility or risk factors, can be used in selecting study cohorts, assessing participant compliance and/or determining agent efficacy. Key features of biomarkers include reliability, precision, accuracy and validity. Not all biomarkers are suitable for all purposes and are likely to be imperfect in any single setting. Judicious selection and matching of biomarkers with agents and study cohorts is required for their effective utilization. A critical but non-dichotomous element of risk biomarkers is their degree of surrogacy. A classification scheme is provided that relates the degree of surrogacy of risk biomarkers to their utility in preventive interventions.

Clinical cancer prevention studies that use disease as an end point are of necessity large, lengthy and extremely costly. Development of the field of cancer chemoprevention is being accelerated by the application of intermediate markers to preclinical and clinical studies. One class of potentially useful biomarkers comes from studies of cancer risks derived from exposure to environmental carcinogens of both endogenous and exogenous origins. Sensitive and specific analytical methods have been developed for detecting and quantifying levels of covalent adducts of several important classes of carcinogens with cellular DNA and blood proteins at ambient levels of exposure. Such biomarkers can be applied to the preselection of exposed individuals for study cohorts, thereby reducing study-size requirements. Levels of these carcinogen-DNA and carcinogen-protein adducts can be modulated by some classes of chemopreventive agents. In this regard, these markers can also be used to rapidly assess the efficacy of preventive interventions such as exposure abatement and chemoprevention. However, the successful application of these biomarkers to prevention trials will be dependent upon prior determination of the associative or causal role of the marker to the carcinogenic process, establishment of the relationship between dose and response, and appreciation of the kinetics of adduct formation and removal.

Primary hepatocellular carcinoma is one of the most lethal and most common cancers in Africa and Asia and is associated with exposure to aflatoxin (AF) B1. To date, many human studies have relied upon presumptive intake data, rather than on quantitative analyses of AF-DNA adduct and metabolite content obtained by monitoring biological fluids from exposed people. Information obtained by monitoring exposed individuals for specific DNA adducts and metabolites will define the pharmacokinetics of AFB1, thereby facilitating risk assessment. In addition, using an animal model based on the differential effects of ethoxyquin on the kinetics of AF-DNA adduct and gamma-glutamyl transpeptidase-positive foci formation, we have data to support the concept that measurement of the major, rapidly excised AFB-7-guanine (Gua) adduct in tissues and fluids is an appropriate dosimeter for estimating exposure status and risk in individuals consuming this mycotoxin.