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This excerpt, from the January 15, 2001 issue of Time magazine, reflects the excitement surrounding pharmacogenomics, a burgeoning field that promises to revolutionize medicine by deciphering the genetic basis of variable drug response in individual people. Pharmacogenomics will provide tailored drug therapy based on genetically determined variation in effectiveness and side effects, thereby allowing the use of medications that would otherwise be rejected because of side effects and encouraging development of new medications for specific genotypic disease subtypes.
How does public health relate to pharmacogenomics? The overriding goal of public health is preventing disease and improving health in the population. Most public health strategies (such as behavior modification and dietary intervention) are not tailored but "one size fits all." Pharmacogenomics, currently focused on developing individualized drug therapies for treating diseases and complications, also has the potential to provide a vast array of tailored interventions to prevent disease. For example, pravastatin may be more effective in lowering blood lipid levels in people with the B1B1 variant of the CETP gene than in other people, which could help to reduce their risk of cardiovascular disease. Pharmacogenomics also offers the promise of targeted primary chemoprevention, for example, by using the drug tamoxifen, which may prevent breast cancer among women with BRCA1 and BRCA2 gene mutations.
Nevertheless, as gene discovery accelerates, it will be important to carefully assess the relative benefit—the value added—of targeted intervention strategies based on pharmacogenomics. The medical and economic benefits offered by targeted interventions must be weighed against the cost of genotyping all individuals in order to direct an intervention to only a few. Consider the case of testing for the factor V Leiden allele, which confers a higher than average risk for venous thrombosis. The use of oral contraceptives by women with factor V Leiden greatly increases this risk. Although genetic testing could be used to identify the presence or absence of the factor V Leiden allele in all women before beginning oral contraceptives, the cost of such testing may be too high compared to the benefit of preventing thrombosis in a few women. The cost-effectiveness of this and similar targeted drug interventions will depend on many factors, including the frequency and severity of the clinical outcome averted, the strength of the genotype-phenotype association, and the prevalence of genetic variants.
For pharmacogenomics to fulfill the promise of targeted interventions, clinical and epidemiologic studies are urgently needed to assess (1) how drug response varies among individuals with different genotypes, (2) what the prevalence of relevant genotypes is in the population and in relevant subpopulations, and (3) whether and to what degree other environmental factors (such as other drugs and diet) interact with genetic factors to influence drug response. Clinical trials and observational epidemiologic studies are crucial for providing us with the population-based data needed to use pharmacogenomics in the practice of medicine and public health in the 21st century. |
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