Christopher Dickey

MOLECULAR EPIDEMIOLOGY IN ENVIRONMENTAL CARCINOGENESIS

Environmental factors such as smoking, diet, and pollutants act in concert with individual susceptibility to cause most human cancers. This article briefly reviews molecular evidence that two types of susceptibility factors--common predisposing genetic traits and young age at exposure--convey heightened risk from certain exposures. Examples are drawn from molecular epidemiologic studies of common environmental carcinogens such as polycyclic aromatic hydrocarbons (PAH) and aromatic amines. Understanding of both genetic and acquired susceptibility in the population will be instrumental in developing health and regulatory policies that adequately protect of the more susceptible groups from risks of environmental carcinogens.

Molecular Epidemiology and Occupational Health

For more than a decade, there has been wide agreement that most cancer results from industrial and environmental exposures (such as tobacco smoke; chemical pollutants in air, water, and food; drugs; radiation; dietary constituents; radon; and infectious agents) acting in concert with both genetic and acquired characteristics.’-6 It has been estimated that without these environmental factors, cancer incidence would be dramatically reduced, by as much as 80-90%.3.5 Cancer risk is strongly influenced by genetic composition, age, ethnicity, gender, immune function, preexisting disease, and nutritional levels, but each of these factors in isolation contributes little to overall cancer risk. Genetic predisposition, for example, in the absence of external environmental influence, probably explains no more than 5% of all cancers in the United state^.^ Thus, most cancer is by nature preventable. Given the multifactorial nature of cancer, a practical approach to reducing the incidence of the disease combines active intervention on two fronts: modifying hazardous lifestyles, such as smoking and diets high in fat and low in protective antioxidants and fibers; and reducing or eliminating exposure to carcinogenic pollutants that pose substantial risks. Molecular epidemiology, a preventive approach that incorporates laboratory methods to analyze environmental and host factors (e.g., genetic polymorphisms), has the potential to give early warning by documenting the preclinical effects of exposure and increased susceptibility to cancer. Thus, molecular epidemiology can flag opportunities to avert cancer through timely intervention. Moreover, biomarker data on the distribution of procarcinogenic changes and susceptibility factors in the population can improve estimation of cancer risk from a given exposure.* Significant exposure to carcinogens occurs for many in the workplace. Such exposures might include industrial or man-made chemicals, pesticides, metals, and fibers (for review, see references 9,lO). Occupationally exposed persons are often faced with the choice between the immediate necessity to work and the long-term avoidance of a possible devastating chronic illness related to their job. Most workers given such a choice will continue to work despite the knowledge that they may be endangering their health. In addition, since most of the industrial chemicals produced