Biomarkers in epidemiology: scientific issues and ethical implications.

Abstract

The current generation of biologic markers have three characteristics that differentiate them from previous ones. These include the ability to detect xenobiotics at concentrations at the cellular and molecular level, to detect earlier biologic changes presumptive of disease or disease risk, and to identify a detailed continuum of events between an exposure and resultant disease. If biomarkers are to enhance cancer epidemiology, they must be valid, reliable, and practical. When these characteristics have not been previously demonstrated, pilot studies should be conducted prior to the primary study. Interdisciplinary communication and collaboration is required so that useful markers are selected and that collection and handling, assay, and interpretation are appropriate. The status of many biomarkers is that they have been developed in the laboratory but lack validation for field use. Validation of a marker for use in a population requires attention to issues of background prevalence, sample size, natural history, persistence, variability, confounding factors, and predictive value. Additionally, practical features such as subject preparation, access to specimens, specimen storage aspects, and costs must be clarified. Ultimately, the use of biologic markers in epidemiologic studies will depend on how well the markers increase ability to reduce misclassification, provide for better interpretation of exposure-disease associations, and increase opportunities for prevention. Validation studies and general research using biomarkers also have clinical, ethical, and legal implications. These range from communicating uncertainty about the meaning of a marker to the kinds of societal response that result when groups or individuals are identified as having an "abnormal" marker frequency. Conceptual and Methodologic IssuesThe scientific literature on biomarkers has been characterized more by attention to issues surrounding the development of assays than by the methodology for their use in epidemiologic research or by their ethical and legal impact. Such emphasis on the analytical is natural in view of the stage of development of markers; however, if markers are to be useful in cancer epidemiology and in human risk assessment, issues related to epidemiological and field studies must be addressed. To be useful in cancer epidemiology, applications of biomarkers should reduce misclassification of exposures and disease, enhance detection of exposure-disease associations, or increase opportunities for intervention. Biomarkers have two particularly useful characteristics: analytical sensitivity and the ability to represent steps in a heuristic continuum between

A longitudinal investigation of selected pesticide metabolites in urine

“…Urinary concentrations of selected metals, pesticides, and polycyclic aromatic hydrocarbons (PAH) or their metabolites have been used to monitor national trends in exposure in many countries, for example the United States (Kutz et al, 1992;Hill et al, 1995a) and Germany (Trepka et al, 1997). Biomarkers in urine may be used to assess exposure in environmental epidemiology studies as well (Schulte, 1992).…”

Biomarkers for Great Lakes priority contaminants: halogenated aromatic hydrocarbons.

“…The magnitude of the serum PCB increase was directly related to the extent of the fish contamination. Similar investigations have shown an increase in blood PCB levels following consumption of PCB-contaminated food can be detected as early as 2 Due to the ubiquitous nature of PCBs in the environment, the majority of humans will have detectable levels of PCBs in blood, adipose tissue, and breast milk. Based on PCB concentrations found in domestically produced foods, it is estimated that the general population in North America will have PCB whole blood values in the range of 0 to 10 pg/kg (ppb) (13).…”

“…Three subclasses of biomarkers have been suggested (2): a) biomarkers of exposure-measurement of chemicals (including metabolites) in body fluids, tissues, or cells or the interaction products between the chemicals and an endogenous substance ( Figure 1); b) biomarkers of effect-morphologic, physiologic, and biochemical changes that have occurred as the result of exposure to xenobiotics (depending on the dose-response relationship, a bioeffective or critical dose can be reached at a target organ/tissue, resulting in an alteration of homeostasis [compensatory responses]; when compensatory responses become overwhelmed, adverse health effects may occur); and c) biomarkers of susceptibility-any factor, usually intrinsic or genetic, that may result in an increased response to exposure. An example of a biomarker of susceptibility in humans is the genetic trait of glutathione-Stransferase (GST) deficiency.…”

Epidemiología y genética: ¿alianza estratégica en el nuevo milenio?

“…No hay duda de que el universo de la epidemiología está cambiando rápidamente, y así habrá de continuar en este nuevo siglo. Tales cambios afectarán no solo a los instrumentos de análisis, sino también a las hipótesis de trabajo a las cuales dichos instrumentos habrán de aplicarse (39)(40)(41).…”