Francis Collins and colleagues articulated a vision for using genomics in disease prevention in a "hypothetical case in 2010."1 In this case, a 23-year-old man named John elects to undergo DNA testing for genes related to several diseases. The results suggest that while John is at lower than average risk for prostate cancer and Alzheimer disease, he is at increased risk for lung and colon cancer, as well as for coronary artery disease. Fortunately, preventive interventions are available to help John reduce his risk of developing each of these diseases. Making this hypothetical case scenario even remotely possible by 2010 will require a concerted public health effort to translate genomic sequence data into new opportunities for disease prevention.
Traditionally, genetic diseases have been perceived as rare conditions resulting from high-penetrance mutations inherited in a Mendelian fashion such as Tay-Sachs disease.2 However, the etiology of common chronic diseases such as cancer, heart disease, and diabetes also has a significant genetic component. In these cases, inheritance is non-Mendelian and complex, making the causal genetic factors difficult to identify. Variants of multiple genes may each contribute a small part of the total risk for an individual. For example, evidence supports a role for common variants of a drug-metabolizing enzyme, N-acetyltransferase, in mediating susceptibility to sporadic bladder and colorectal cancer.3 Because these variants only become risk factors in the presence of bladder or colon carcinogens, they alter an individual's risk only slightly, but they may be responsible for a large number of cancers in populations that are exposed to carcinogens.3
Currently, because the presence of common genetic polymorphisms alone cannot accurately predict disease susceptibility, genetic tests for these variants rarely furnish information that can be used in prevention. The hope for the future is to learn what combination of gene variants and environmental factors predispose people to disease, and to use this information to prevent disease. For example, people who have the gene variant that codes for the "slow-acetylator" form of N-acetyltransferase, and who have a specific combination of other, as yet unidentified, risk factors, might be counseled to avoid working with bladder carcinogens like aniline dyes. In the future this model may provide targeted intervention and prevention. The US Centers for Disease Control and Prevention (CDC) has detailed the essential public health functions for genetics to play a role in disease prevention.4
Population based epidemiological studies are needed to learn the prevalence of gene variants that predispose people to disease, the burden of disease and death caused by these diseases, and the prevalence of disease-causing environmental exposures in genetically susceptible people. These studies are also needed to identify how environmental factors interact with genetic factors to cause disease. Such studies will often take years to complete, although in some cases, the information can be obtained retrospectively using incident case-control studies that are derived from population-based registries of diseases.5
For genetic tests to have practical value, they must be evaluated for their sensitivity, specificity, and positive predictive values in relation to measured genotypes (analytic validity) and specific health outcomes (clinical validity). To calculate these essential parameters, information about the prevalence and penetrance of disease-associated gene variants is required from population-based studies. When this information is available, genetic tests may improve the clinical predictive values of traditional risk factors for disease. For example, hypercholesterolemia is an independent risk factor for heart disease that can be treated with statin drugs.6 Because nearly one third of the US population has hypercholesterolemia, an important public health priority would be to optimize the cost-effectiveness of statin therapy. Genetic testing may one day identify the population that will benefit most from these drugs.
As more genetic tests are developed and marketed, it will be important to evaluate the value they add to existing medical and behavioral interventions. Population research will facilitate this evaluation of genetic testing and thereby prevent its misuse while helping to realize its benefits. Although new developments in genomic medicine will give physicians new tools for promoting health, preventing disease, and managing illness, they will also create a new responsibility to ensure they are used wisely and well.
Steinberg KK, Gwinn M, Khoury MJ. The Role of Genomics in Public Health and Disease Prevention. JAMA. 2001;286(13):1635. doi:10.1001/jama.286.13.1635-JMS1003-3-1