Molecular epidemiology of human cancer: biomarkers of genotoxic exposure and susceptibility.

The new field of molecular epidemiology investigates the link between toxic exposure and an associated health effect by defining presumptive intermediate stages in the development of the disease based on known mechanisms. In the development of malignancy, these steps may involve exposure to known mutagens and carcinogens, internalization and potential metabolism of a chemical agent, characterization of the interaction of the agent at its site of action (usually DNA), characterization of induced preneoplastic changes, and, in certain instances, early detection of the cancer itself. These processes can be monitored through biomarkers specific to each of the steps in the progression toward disease using any of the host of applicable techniques now available. An overview of such techniques is presented, with emphasis on techniques offering insight into the malignant process. Evidence is presented suggesting that although there are many potential contributing mechanisms to carcinogenesis, mutagenesis remains the dominant driving force behind the process. Several methods of monitoring mutation have shown promise as predictors of cancer incidence. These methods might also be used as monitors of agents designed to intervene in the process to prevent the development of overt disease.