Selection and validation of biomarkers for chemoprevention: the contribution of epidemiology

Abstract

This chapter considers the epidemiological contribution of DNA adducts as an example of markers for use in chemoprevention studies, and highlights the potential biases inherent in the conduct of epidemiological studies with molecular markers. Although adducts have been interpreted mainly as biomarkers of exposure, 'bulky' DNA adducts such as those measured by 32P-postlabelling or ELISA in white blood cells are more correctly interpretable as markers of cumulative unrepaired DNA damage. The latter concept can prove useful in cancer epidemiology, since it is consistent with existing knowledge on the importance of duration of exposure in the etiology of chemically-induced cancers. Increasing evidence suggests that in addition to prolonged exposure to genotoxic chemicals, inter-individual variability in carcinogen metabolism and DNA repair is predictive of cancer risk. Also from this point of view, measurements of 'bulky' DNA adducts can be useful as biomarkers for studies in populations, since they express the amount of carcinogen linked to DNA after repair, taking into account individual repair capacity. Finally, we suggest a theory of causality based on the work of Wesley Salmon and the concept of 'propagating mark', which is particularly attractive for molecular epidemiologists.