Validation of biomarkers as early predictors of disease

The development and validation of biomarkers that link environmental exposu res to the pathogenesis of human disease is a leading priority in the field of environmental research. The validation of biomarkers as early predictor s of clinical disease can enhance health risk assessment and contribute to effective new disease prevention policies in environmental and occupational settings. The process of validating biomarkers involves dealing with a ran ge of characteristics that include the intrinsic qualities of the biomarker , its determinants, and the analytic procedure. We discuss here a three pha se approach to validation. The final phase, consisting of longitudinal stud ies, is reached after the biomarker has been determined to be technically r eliable and after the effect of external variables on the association with the outcome has been evaluated. We provide some examples of biomarkers repu ted to be early predictors of cancer and cardiovascular disease (CVD). We t hen present original data to support the potential of DNA adducts to predic t cancer and show, through re-evaluation of the Italian database on cytogen etic biomarkers, a lack of association between the frequency of chromosomal aberrations in circulating lymphocytes and CVD mortality rates - a finding that should not be considered conclusive. In general, whenever a biomarker has been determined to be a valid predictor of disease, it should be used in risk assessment and public health policy. (C) 2001 Elsevier Science B.V. All rights reserved.