The light at the end of the tunnel for chemical-specific biomarkers: daylight or headlight?

Chemical-specific biomarkers: the challenge and goals The use of chemical-specific biomarkers for identifying stages in the progression of development of the toxic effects of environmental agents has the potential for providing important information for critical regulatory, clinical and public health problems (1,2). Since the development of a paradigm for molecular biomarkers by a committee of the National Research Council over a decade ago, some progress has been made in applying such chemical biomarkers to specific environmental situations that may be hazardous to humans, as exemplified by the study of aflatoxins discussed in detail below. As in many areas of science, however, the initial excitement at being able to measure a specific entity has been replaced by the challenge of how to interpret the results. This dilemma is exacerbated by the complexities introduced through the interactions between genes and environmental factors that underlie most human disease. For a molecular biomarker paradigm to guide public health issues, molecular epidemiologists must devise and follow careful strategies for validation, application and dissemination of information about these biomarkers to the public. The major goals of environmental chemical-specific biomarker research are to develop and validate biomarkers that reflect specific exposures and predict disease risk in individuals. Presumably after environmental exposure each person has a unique response to both dose and time to disease onset. These responses will be affected both by intrinsic (genetic) and by extrinsic (such as dietary) modifiers. It is assumed that biomarkers that reflect the mechanism of action of an environmental chemical will be strong predictors of an individual’s risk of disease. It is also expected that these biomarkers can more clearly classify the status of exposure of individuals, local communities and larger populations. Misclassification of exposure status is a major contributor to the insensitivity of many epidemiological investigations. Further, biomarkers should provide an objective measure for determining the effectiveness of interventions to lower exposure and risk. These studies should help elucidate the molecular processes of chemically induced human disease and underlying susceptibility factors. Finally, biomarkers should help sort out the interactions of multiple agents and multiple exposures and their relation to disease outcomes. These overall goals are summarized in Table 1.