The future of personalized medicine- will it be based on pharmacogenetics?
It has been quite awhile since my last post, partially due to the fact that over the last 9 months I had the opportunity to work at Coriell Institute for Medical Research as part of a team who had established the Coriell Personalized Medicine Collaborative cohort study. As a genetic epidemiologist, I was hired to review the scientific literature and assess what genetic variants (mainly SNPs) were associated with particular chronic diseases which were considered actionable (i.e, modifiable in terms of prevention or treatment options). In addition to acquiring and summarizing risk information for the genetic polymorphisms, risk estimates for lifestyle, family history and other environmental risk factors were needed to provide the participants in the study a comparative estimate for their genetic risk. In almost all cases, the risk of non-genetic risk factors for chronic disease was much higher than the risk from a particular genetic variant. This is not surprising since most of the genetic studies (using GWAS to detect associations) of chronic disease have not found large risks from a single variant. Usually risk estimates are quite small in effect ranging from a 10%-30% increased risk per allele. Comparatively, factors like smoking and obesity can increase the risk for a chronic disease 2-fold (200%) or more. Whether the use of multiple variant models will show significantly larger effect sizes has not been shown or replicated for chronic diseases in the literature as of yet.
One of the more promising areas of personalized medicine may be the utility of pharmacogenomics in treatment or prevention of disease. One of the successful examples of a pharmacogenomic application in medicine has been the use of Herceptin on HER2+ expressing breast tumor cells. To illustrate how personalized medicine can impact the success of medical treatment a recent editorial in Forbes was published by a biotech representative, Adriana Jenkins, whose last wish was to ask Congress and pharmaceutical companies to support more personalized medicine strategies in the future because the development of Herceptin extended her life by 9 years. Other examples of pharmacogenetics which have the potential to impact medical practice include warafarin dosing with genetic variants in VKORC1 and CYP2C9 genes and clopidogrel metabolism with variants in CYP2C19 that produced an FDA to create a warning label. But research into these associations and their clinical utility are just beginning. Pharmacogenomics could play a significant role in tailoring medicines to particular individuals in both increasing efficacy and reducing or preventing adverse drug reactions.
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