Biomarkers

Types of Biomarkers

Biomarkers may take the form of exogenous compounds (e.g., absorbed chemicals, pesticides, food derivatives, metals), whose presence can be detected and quantified in biologic media, as well as measures of endogenous biologic substances, such as nucleic acids, proteins, and lipids. Biomarkers may be measured from any number of biologic media, including blood, urine, hair, feces, sputum, nails, and other body fluids and tissues. Table 1 lists the types of different biomarkers that have been used in epidemiologic assessments.

Uses of Biomarkers in Epidemiologic Studies

For purposes of epidemiologic research, biomarkers can be broadly grouped into three categories: (1) biomarkers of exposure, (2) biomarkers of effect, and (3) biomarkers of susceptibility. These categories are defined by their position in the spectrum of the exposure-outcome relationship. It is important to note that many biomarkers may play multiple roles, depending on the particular research question being posed. For example, circulating low-density lipoprotein (LDL) may be both a measure of exposure (as a risk factor for coronary heart disease) and a measure of outcome (in a trial of a lipid-lowering therapeutic) within two different studies.

When evaluating exposures, a distinction can be made between the external dose, or the amount that the subject is physically exposed to in their immediate environment, and internal dose, or the total amount of exposure that the subject has absorbed internally over a period of time. Depending on the measure, biomarkers of exposure can reflect the internal dose at any stage along its pathway, from the initial unaltered but absorbed exposure to a biologically altered and metabolized form delivered to tissues, and finally to the chemically and/or structurally altered biologic substance as a result of exposure.

Biomarkers identified and measured in body tissues or fluids that are either unchanged or metabolically altered are considered biomarkers of internal dose, while biomarkers of biologically effective dose are markers measured in target or surrogate tissue that reflect the interaction of the absorbed exposure with a subcellular target. Examples of internal and biologically effective dose biomarkers are given in Table 2.

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