The role of molecular epidemiology in cancer prevention.

Risk of cancer is determined by the complex interaction between "environmental" exposures and genetic and nutritional factors that modulate response to carcinogenic insults. Here, the term "environmental" encompasses lifestyle, occupation, and the ambient environment. As a promising approach in cancer prevention, a number of biologic markers are currently being evaluated in terms of their ability to identify harmful exposures and populations at risk in time to effectively intervene. These biomarkers are reflective of the molecular dose or early effect of carcinogens (such as DNA or protein adducts, gene or chromosomal alterations and oncogene activation) or they provide information on potential susceptibility (such as the genetically or nutritionally determined handling of carcinogens). Techniques as diverse as immunoassays, 32P-postlabelling and gas chromatography-mass spectroscopy (GC/MS) are being deployed to measure DNA and protein adducts in cells and tissues from persons with occupational, community or lifestyle-related exposure to chemical carcinogens. Signal changes in target oncogenes and tumor suppressor genes are also being investigated in heavily exposed, "healthy" populations and in lung cancer cases and controls using current molecular biologic techniques. Inherited predisposition to lung cancer is being evaluated through such assays as aryl hydrocarbon hydroxylase (AHH), glutathione activity and restriction fragment length polymorphism. A review of recent studies using a panoply of biomarkers provides a departure point for recommendations for future, integrated molecular epidemiologic studies of cancer.