Biological markers can be conceptualized in terms of categories of markers that form a continuum representing a sequence of events from exposure to disease. These categories include markers of internal dose, biologically effective dose, early response, and disease. Outside of this sequence are susceptibility factors that can act at any point along the way to modify the effects of external exposures on disease outcomes. Examples of the use of these different types of markers in epidemiologic research are provided. There are many factors that one must consider when selecting a biological marker for use in an epidemiologic study. These factors include: the objectives of the study, the availability and specificity of potential markers, the feasibility of measuring the markers in various biological media, the invasiveness of the techniques necessary to measure the markers, the amount of biological specimen needed for analysis, the time to appearance of the markers in the biological media, the persistence of the markers in biological media, the variability of marker levels within and between individuals, the stability of markers in storage, as well as the cost, sensitivity, specificity, and reliability of the assays used to measure the markers. Each of these characteristics is discussed. The usefulness of biological markers in an epidemiologic study depends on the objectives of the study and whether the properties of the markers fulfill the objectives of the study in a feasible and cost-effective manner.
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