lunes, 1 de abril de 2013

CDC - Blogs - Genomics and Health Impact Blog – On Spinning Wheels and Genomes Revealed:

CDC - Blogs - Genomics and Health Impact Blog – On Spinning Wheels and Genomes Revealed:

On Spinning Wheels and Genomes Revealed:

Categories: genomics
Muin J Khoury, Director, Office of Public Health Genomics, Centers for Disease Control and Prevention

Sequencing is No Longer a Sleeping Controversy

sleeping beautyIn the classic Disney version of the fairy taleExternal Web Site Icon, Sleeping Beauty is hidden in the woods to protect her from the knowledge of an evil curse… but when she later pricks her finger on a spinning wheel, she falls under a fairy’s spell…
Unlike the mythical magic of centuries old stories, modern science is changing our lives in ways that are anything but fantasy. Advances in whole genome sequencing (WGS) promise to reveal fundamental information about our risks for various diseases. By definition WGS includes an enormous amount of data: six billion base pairs in a human’s genomeExternal Web Site Icon. Unfortunately, we do not yet know what to do with the great majority of these data points, a fact that will become even more important in the next decade. For as sequencing technology becomes less and less expensive, it could soon be more economical and practical to simply conduct WGS ratherExternal Web Site Icon than individual tests that assess one or a few genetic variants.
Two publications have now raised awareness of the potential controversies associated with the anticipated integration of WGS into clinical and public health practice. The most recent was the American College of Medical Genetics report ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing. Adobe PDF fileExternal Web Site Icon The report argued that persons whose genomes are sequenced for any medical reason should be informed, via their healthcare providers, about variants in 57 genes that put them at risk of preventable diseases – a form of “opportunistic screening”. The second article is a commentary in the journal Genetics in Medicine entitled: We Screen Newborns Don’t We?: Realizing the Promise of Public Health GenomicsExternal Web Site Icon. James Evans and coauthors argue for a public health approach to assess the feasibility of active population screening for selected rare genomic variants to find millions of affected people who are at risk of preventable diseases such as cancer and heart disease – a model not too dissimilar from newborn screening. It is not clear from these two reports whether or not the list of genes recommended for opportunistic screening in medical settings is the same as the list proposed for active population screening.
With much of the genome revealed, how can we benefit from such information while we likewise protect ourselves from its potential harms? The publications are igniting discussion about our readiness, or lack thereof, to integrate WGS into health care and disease prevention. In addition, they point to significant ethical, legal, and social implications of releasing genetic information, incidental or otherwise, back to patients or healthy persons, when the clinical validity and utility of this information have not been established. Indeed, ACMG acknowledges that “there are insufficient data on clinical utility to fully support [its] recommendations”. As a test in clinical practice, our office classifies WGS as a “tier 3” application due to critical gaps in our knowledge on analytic validity, as well as clinical validity and utility.
Furthermore, interpretation of genetic variants is highly contextual and is based on age, family history, clinical presentation, and environmental factors. For example, for BRCA testing, the US Preventive Services Task Force recommended that women with increased family history risk for hereditary breast and ovarian cancer be offered genetic counseling for testing while recommending against routine BRCA screening for women without family history riskExternal Web Site Icon. Similarly, The Task Force recommended against testing for hereditary hemochromatosis in the general populationExternal Web Site Icon. More recently, the EGAPP working group recommended against testing for Factor V LeidenExternal Web Site Icon for adults with idiopathic venous thromboembolism and their family members, and they found insufficient evidence for testing for genetic risk assessment for diabetesExternal Web Site Icon and for cardiovascular disease in the general populationExternal Web Site Icon.
As important, there are significant ethical concerns about the return of genetic information, especially for children. True informed consent is a must but may be difficult to achieve in practice. Meanwhile, proponents argue that people have a right to know their own biological data and make their own decisions. Others argue that genomic data are not really information if we don’t know what they mean. In addition to psychosocial and medical harms, premature use of genetic information in health care could lead to a cascade of increased health care costsExternal Web Site Icon resulting in further testing and unproven interventions. These issues are not newExternal Web Site Icon but are increasingly coming to the forefront as the time to deal with the reality of the genome draws nearer to implementation in practice.
In our opinion, these significant concerns emphasize the importance of a policy framework to guide an evidence-based approach to incorporate WGS technology into health care and public health. A time is coming when the decision to perform this or that specific DNA test could no longer be relevant. If DNA testing is needed for any medical reason, pragmatic economics could dictate that WGS is conducted. Patients and their families, under the right scenarios, could benefit from receiving incidental findings with demonstrated clinical utility and with appropriate patient education and counseling. However, even established tests, such as those for BRCA and Lynch syndrome with demonstrated clinical utility in certain clinical situations, present challenges when testing for WGS in unselected individuals.
Fortunately, like fairy tale spells, genes do not necessarily determine fate. However, this is not the time to “hide” important information, supported by evidence of clinical utility, that could be revealed by WGS in health care and disease prevention. Genetic counselors and other health care providers must be ready to effectively communicate to patients and families what we know and what we don’t know. Most importantly, we must avoid “spinning wheels” by debating the issues without a firm evidentiary foundation on which to base implementation of WGS in practice. In order to understand the utility of testing for specific genetic variations in our genome to improve the health of individuals and populations, we must rely on family and population-based research, including clinical trials.
As for those who have long taken a “wake me when we get there” attitude to genomic medicine: take heart, for the “prince” may be near at hand…
spinning wheel

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