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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