Use of carcinogen-DNA and carcinogen-protein adduct biomarkers for cohort selection and as modifiable end points in chemoprevention trials.

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.