October 26, 2009 (檀香山) — 在美國人類基因協會(American Society of Human Genetics，ASHG)第59屆年會的記者會中，人類遺傳學的領導者探究個人化醫療的未來以及將基因學研究轉為健康照護實務的方法。提出了在預防、診斷和治療方面的進步，以及從基因角度看風險承擔行為、藥物效果、病患對基因檢測結果的反應等。
美國人類基因協會(American Society of Human Genetics，ASHG)第59屆年會：記者會。發表於2009年10月21日。
The Future of Healthcare Practice: Predictive, Preventive, and Personalized
By Jacquelyn K. Beals, PhD
Medscape Medical News
October 26, 2009 (Honolulu, Hawaii) — Leaders in human genetics looked to the future of personalized medicine and ways to translate genetics research into healthcare practice, during a briefing here at the American Society of Human Genetics (ASHG) 59th Annual Meeting. The panel described advances in prevention, diagnosis, and treatment, and the genetic aspects of risk-taking behavior, medication effects, and patient response to genetic test results.
Moderator Edward McCabe, MD, PhD, physician-in-chief at UCLA Mattel Children's Hospital, founder and director of UCLA Personalized Genetics Medicine Center in Los Angeles, California, and 2009 president of ASHG, observed that "to be personalized, medicine must also be predictive and preventive."
One benefit of personalized medicine is prevention of adverse drug effects. As an example, Dr. McCabe called Vioxx "an outstanding drug for better than 95% of patients, but for the few percent who suffer side effects, it's a terrible drug."
Scientists might previously have dismissed such results as statistical variation, but geneticists now recognize that these "statistics" reflect a small percentage of patients with a gene or genes leading to a given adverse effect. "We're learning that more and more is genetic," said Dr. McCabe. "And we need to understand it so that we can improve healthcare and how we give drugs to people."
Genetic screening that uses microarrays must be translated effectively, efficiently, and rapidly from research into clinical practice. A recent paper in the New England Journal of Medicine reported screening patients with Job's syndrome (hyper-IgE syndrome). More than 50% had a deletion in DOCK8 detectable by microarray analysis. "If you have a patient with Job's syndrome, the first test that you should run is one of these microarrays, looking for that deletion," Dr. McCabe advised.
All diseases have a genetic component, said Dr. McCabe. Some people might add "with the exception of trauma," but people are beginning to think that even risk-seeking behavior has genetic factors. With genetic information, "we can develop innovative ways to diagnose disease and screen for health risks and early symptoms, to be predictive, preventive, and personalized," Dr. McCabe summarized.
Many clinicians say they have practiced personalized medicine their whole career, but "we didn't have the tools we have now," said panel member Alan Guttmacher, MD, acting director of the National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH) in Bethesda, Maryland.
Dr. Guttmacher described a longstanding debate within organized medicine as to whether a woman in her 40s should have an annual mammogram. If she has genetic indications of increased breast cancer risk, perhaps she should start annual mammograms in her 30s, yet other women could start screening in their 50s. "But we're not yet able to recognize the differences among those women," said Dr. Guttmacher.
A major scientific breakthrough, covered in Science in 2007, has been the era of genome-wide association studies. These studies have yielded information about hundreds of genes with an impact on scores of diseases, and reveal a lot about the mechanisms and biology of diseases. "It's been a wonderful time; it brings interesting challenges and rich research opportunities," said Dr. Guttmacher.
NHGRI is currently investigating individuals' reactions to the results of genetic testing. A BRCA1 mutation, for example, is known to increase the risk for breast and ovarian cancer. Some women with the mutation understand their increased risk; others, given the same information, decide never to be tested again. Primary care providers must be able to handle these situations, and geneticists should provide them with good information.
A serious issue in genetic testing is the "worried well." Panel member Roderick McInnes, MD, PhD, talked about people whose genomic testing shows they are heterozygous for ApoE4, which is associated with an increased risk of developing Alzheimer's disease. Yet 50% to 75% of people carrying this allele never get Alzheimer's, and no current treatment can slow the disease. Dr. McInnes is professor of human genetics and biochemistry at McGill University in Montreal, Quebec; scientific director of the Institute of Genetics, Canadian Institutes of Health Research in Toronto, Ontario; and 2010 president-elect of ASHG.
"In most cases, people who hesitate to act on [getting genetic testing] may be quite wise," suggested Dr. Guttmacher.
"Personalized medicine is nothing new," Dr. McInnes observed. Those who deal with single-gene diseases have been practicing this kind of medicine for decades. Children in developed countries are screened shortly after birth for blood levels of phenylalanine. Genetic studies have identified a minimum of 5 or 6 genes that, when mutated, result in increased phenylalanine.
The most common treatment is to put children on a low-phenylalanine diet to prevent brain damage. However, 1 of these mutations is effectively treated by taking a pill. "For patients in whom the mutant protein is still made, you can sometimes give very high doses of tetrahydrobiopterin?.?.?. and that will restore very small amounts of enzyme activity to the mutant protein," Dr. McInnes told Medscape Pathology. This genetic understanding saves a patient from years on a severely restricted diet.
"Pharmacogenetics is an attractive target because the healthcare system is amenable to that," said Leslie G. Biesecker, MD, chief and senior investigator of the Genetic Disease Research Branch, NHGRI, NIH, commenting to Medscape Pathology on this issue: "Because you don't have to radically change the healthcare system to do that."
"We also know that the clinicians (myself included) are phenomenally inefficient at prescribing, monitoring, and using the optimal drug for each patient. It's all trial and error. It wastes?.?.?. resources, it undertreats some patients, and it causes a lot of side effects in other patients, and all that stuff costs money, Dr. Biesecker said. "If we could even partially fix that problem using pharmacogenetics and whole-genome technology, there would be enormous potential healthcare cost savings, not to mention the sometimes irreversible consequences of severe side effects."
Dr. McCabe, Dr. Guttmacher, Dr. McInnes, and Dr. Biesecker have disclosed no relevant financial relationships.
American Society of Human Genetics (ASHG) 59th Annual Meeting: Press briefing. Presented October 21, 2009.
