8.34 - Molecular Biomarkers

Abstract

The identification, development, validation, and application of molecular biomarkers reflecting events from environmental and endogenous exposures to the diagnosis of clinical disease have rapidly expanded our knowledge of the mechanisms of pathogenesis and have provided opportunities for devising improved tools for disease treatment and public health prevention. This field of research has been most extensively explored in cancer, but in recent years molecular biomarkers reflecting the progression pathways in developmental diseases, as well as cardiovascular disease and neurological disorders among others, have been rapidly increasing (Castellanos and Serena, 2007; Wallace, 2005; White and Van Eyk, 2007). The integration of molecular biomarkers into epidemiology involves the incorporation of an array of molecular, cellular, and other biochemical measurements into individual and population studies exploring the etiology, prevention, and control of health risks faced by diverse human populations (Hulka, 1991; Poirier et al., 2000; Wogan, 1992). The application of validated biomarkers to traditionally descriptive epidemiological studies helps to delineate the continuum of events between an exposure and resulting disease. Epidemiology is no longer a science of mathematical “association” but is now a science where we can molecular mechanisms underlying disease are studied in humans. The sensitivity of these tools also helps to identify the biological response to lower dose, chronic exposures to specific xenobiotics and reveal individual risk at earlier time points in the natural history of diseases. Collectively, the sensitivity and specificity of these molecular biomarkers contribute to a reduction in the misclassification of exposure-health relationships and enhance individual and group risk monitoring and assessments. These investigations also reveal toxicologic mechanisms by which an exposure and a disease are related (Schulte, 1993). A unique feature of molecular biomarker-based epidemiological studies is the interdisciplinary collaboration among population and field scientists and laboratory scientists from various disciplines, such as epidemiology, toxicology, molecular biology, genetics, medicine, immunology, biochemistry, pathology, and analytical chemistry. Since the analytic measurement of biomarkers is critical to molecular epidemiological studies, special attention needs to be paid to the collection, handling, and storage of biological specimens, as well as development and validation of analytical methods (Hattis and Silver, 1993).