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作者：Jacquelyn K. Beals, PhD  
出處：WebMD醫學新聞

　　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。
　　
　　會議主持人、UCLA Mattel兒童醫院內科主任、UCLA個人化基因醫學中心發起人暨主任、ASHG 2009年理事長、Edward McCabe醫師觀察發現，為了達到個人化，醫學上必須可以預測和預防。
　　
　　個人化醫療的好處之一是預防藥物副作用。McCabe醫師舉例，Vioxx是一個對95%以上病患都很好的傑出藥品，但是對於少數飽受其副作用之苦的病患來說，它是很可怕的藥品。
　　
　　科學家以前可能反駁這類結果、視為統計上的變異，但是遺傳學者現在將這些統計差異視為反映出少數病患因某個或某些基因而造成這些副作用。McCabe醫師表示，我們對遺傳學的認識越來越多，我們需瞭解它，以改善健康照護以及給藥。
　　
　　使用微陣列分析進行基因篩檢必須有效、且高效率而迅速地從研究轉入臨床實務。最近在新英格蘭醫學期刊中，一篇論文指出Job氏症(高免疫球蛋白E症候群)患者的篩檢。微陣列分析發現超過50%患者在DOCK8有一個缺損。McCabe醫師建議，如果你有一個Job氏症病患，第一個要做的檢查就是這些微陣列分析之一，看有沒有這個缺損。
　　
　　McCabe醫師表示，所有的疾病都有其基因組成。有些人可能會說「除了創傷之外」，但是人們開始思索，即使是尋找風險的行為也有基因因素。McCabe醫師總結道，藉由基因資訊，我們可以發展診斷疾病和篩檢健康風險及早期症狀的全新方法，而可以預測、預防和個人化。
　　
　　小組成員之一、國家健康研究中心、國立人類基因圖研究中心執行主任Alan Guttmacher醫師報告指出，許多醫師表示，他們一直都在從事個人化醫療，但是我們過去沒有現在這些工具。
　　
　　Guttmacher醫師提出長久以來的一個論辯，40歲左右的婦女是否應該開始每年的乳房攝影檢查。如果她的基因上有增加乳癌的風險，或許她在30多歲就應該開始每年進行乳房攝影檢查，而其他婦女則可能在50多歲才開始檢查。Guttmacher醫師表示，但是我們還無法確認這些婦女之間的差異。
　　
　　2007年的Science期刊發表了一個重要的科學突破，是基因圖關聯研究的新紀元。這些研究獲得數百個基因對疾病之影響的資訊，發現許多疾病的機轉與生物學知識。Guttmacher醫師表示，這是美好的時光；帶來許多有趣的挑戰和豐碩的研究機會。
　　
　　NHGRI目前在研究個人對基因檢測結果的反應。例如已知BRCA1突變會增加乳癌和卵巢癌風險，有些有此突變的婦女知道她們的風險增加；其他在給予同樣的資訊之後，決定不要再度檢測。一線照護提供者必須可以處理這些狀況，遺傳學家應提供他們這些可用資訊。
　　
　　基因檢測的一個嚴肅議題是「困擾的正常人(worried well)」。小組成員之一、Roderick McInnes博士提到基因檢測顯示為ApoE4異型合子(發生阿茲海默氏症之風險增加)的人，但是，有此合子者有50%- 75%並未發生阿茲海默氏症，目前也無可以延緩此症的治療方式。McInnes博士是魁北克McGill大學生化與人類基因學教授；加拿大健康研究院、基因研究中心科學主任；ASHG的2010年理事長候選人。
　　
　　Guttmacher醫師認為，多數案例中，猶豫是否進行基因檢測的人也許是相當明智的。
　　
　　McInnes博士觀察發現，個人化醫療現在不是新聞。單一基因之疾病的個人化醫療處置已經進行數十年。已開發國家的小孩在出生後不久就進行血中苯丙氨酸檢測。基因研究確認至少有5或6種基因之突變會造成苯丙氨酸增加。
　　
　　最常見的治療是讓病童使用低苯丙氨酸飲食以避免腦部損傷。不過，這些突變之一可以用藥物有效治療。McInnes博士向Medscape Pathology表示，對於繼續製造突變蛋白質的病患，有時候你可以給予極高劑量的四氫基喋呤(tetrahydrobiopterin)，將可以恢復少量對突變蛋白質有活性的酵素。這種基因學上的瞭解，可以讓病患的嚴格限制飲食減少好多年。
　　
　　NIH之NHGRI的遺傳疾病研究小組資深研究員暨主任Leslie G. Biesecker醫師受Medscape Pathology之邀對此議題發表評論時表示，藥物基因學是一個有吸引力的目標，因為健康照護體系願意進行，也因為你不必徹底改變健康照護體系來達到它。
　　
　　Biesecker醫師表示，我們都知道醫師們(我自己也是)在處方、監控，為每個病患使用適當藥物上，實際上是沒有效率的，都是嘗試與錯誤。浪費了資源、某些病患治療不足、某些病患出現許多副作用、浪費金錢。如果我們可使用藥物基因學和全基因圖科技來解決部份問題，將有很大的潛力節省健康照護費用，何況有時候嚴重副作用還伴隨著不可逆的後遺症。
　　
　　McCabe醫師、Guttmacher醫師、McInnes醫師與Biesecker醫師皆宣告沒有相關財務關係。
　　
　　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.