ons to prevent disease, death or disability (e.g., phenylketonuria or PKU), public health agencies cannot play a role in promoting the use of genotypic prevention as a method to improve the public's health.
Another philosophical issue in the integration of genetics into public health is what defines a genetic condition. Geneticists often make a distinction between single-gene disorders and susceptibility genes that are disease risk factors along with other genes and environmental exposures involved in disease development. This distinction is embodied in the concept of genotype penetrance. The distinction tends to fade when one realizes that all human disease is the result of interactions between genetic variation and the environment (broadly defined to include dietary, infectious, chemical, physical and social factors). Even many of the classical single-gene metabolic disorders are the result of a deficiency in a nutritional enzyme combined with dietary exposure to one or more chemicals (e.g., phenylalanine and phenylalanine hydroxylase deficiency in PKU; and iron intake and mutations in the HFE gene in hereditary hemochromatosis (17). As Rothman puts it, "It is easy to show that 100% of any disease is environmentally determined and 100% is genetically determined as well. Any other view is based on a naive understanding of causation" (21). Perhaps the wide range of penetrance with respect to clinical disease could be due, in part, to variations in the prevalence of interacting cofactors (e.g., other genes and modifiable risk factors). Universal exposure of newborn infants to phenylalanine through their diets leads to a high incidence of mental retardation among those who inherit a deficiency in phenylalanine hydroxylase.
If we accept the fundamental premise that genetic variation is associated with all human disease, there is no compelling reason to label a disease as genetic or not. For example, one can label hereditary hemochromatosis as an iron overload disorder resulting from the interaction between an inherited variation in iron transport, iron intake and iron loss. Similarly, breast cancer in some individuals could result from the interaction between an inherited mutation in the BRCA1 gene and yet-to-be-described cofactor(s), including other genes and modifiable risk factors. When this book's authors refer to "genetic disorders," they are usually referring to conditions in which a single gene with high penetrance or a chromosomal abnormality have been implicated. It is implicit, however, that genetic factors do play a role in the etiology of virtually all human diseases, even those that are traditionally not thought of as "genetic" (e.g., infectious and occupational diseases).
Thus, an important theme of this book is the need to identify the modifiable risk factors for disease that interact with the genetic variation and that may be used to help target preventive interventions. Recognition of the need to apply knowledge about the interaction between environment and genetics to health care has been described in the popular press (22).
Finally, an inherent assumption in our discussion of the future of genetics in public health is that much of the delivery of genetic tests and services for disease prevention and health promotion, including adequate family history assessment and genetic counseling, will be done within the context of the broader healthcare system. Managed care organizations will play an important role in integrating genetic services into disease prevention and health promotion activities.
Framework for Integrating Genetic Discoveries into Public Health Functions
A framework for applying essential public health functions in evaluating the relevance of gene discoveries to disease prevention and health promotion was developed as part of the CDC's strategic plan for genetics and public health (11). This framework encompasses four essential public health functions and three critical issues that affect each function (Table 3). The rest of this book is largely organized according to these public health functio