A Need to Know Basis
Nov 01, 2013 01:08PM ● Published by Cate Reynolds
By Lisa A. Lewis
When Angelina Jolie announced in May that she had undergone a preventative double mastectomy after learning she carries a mutation of the BRCA1 gene, which significantly increases her risk for developing breast cancer and ovarian cancer, her story was highly publicized—emphasizing the importance of genetic testing and its potential ability to save lives. Testing for specific genes that can cause diseases has been performed for several years. Like Jolie, you may also have undergone genetic testing, especially if you have a family history of a particular illness. As advancements continue to be made in genetic testing, a relatively new technology (called whole genome sequencing) has become increasingly common, and it’s changing the scope of genetic testing.
Whole Genome Sequencing 101
Whole genome sequencing is a procedure that analyzes your entire DNA—all of your genes, rather than just a specific gene. The test, which can be performed with a blood sample, indicates which genes carry a predisposition for disease, revealing your susceptibility to a wide range of medical conditions and providing your doctor with potentially life-saving information. (Although having a genetic predisposition for a disease increases your risk, it doesn’t mean you will develop the disease.)
“We’ve been doing clinical gene sequencing for many years,” says Michael S. Watson, Ph.D., FACMG, executive director, American College of Medical Genetics and Genomics (ACMG). “What’s new is sequencing the entire genome. The game changer is the combination of having a crude human genome sequence and the computer power to analyze and interpret the sequence data. Now we can do the entire genome instead of one gene at a time. We can test for or target a specific gene variation, or we can sequence a region to see what’s there.”
Indeed, gene sequencing has a long history. Watson says the first report of a molecular test for a genetic disease was around 1976 when Y.W. Kan tested for the sequence variation that causes sickle cell disease. Over time, more genes were associated with diseases, and tests were developed for them. Through the Human Genome Project, the technologies underlying current medical sequencing were developed, and the first draft sequence of the entire genome was announced in 2003.
Scientists can now test for more than 2,200 genes that cause disease, including hereditary breast cancer, colon cancers, neurofibromatosis (elephant man disease), cardiovascular diseases (aortic aneurysm and cardiomyopathy), familial hypercholesterolemia (very high levels of cholesterol), and many more.
The Controversy: Who needs to know what?
But despite its benefits, whole genome sequencing is still a source of controversy. Concerns include the cost—Jolie revealed that testing for breast cancer susceptibility genes costs more than $3,000—as well as insurance and privacy issues.
“Whole genome and exome [part of the genome] sequencing are expensive, although the cost of the actual sequencing is dropping as the technology gets more efficient,” says Megan Allyse, Ph.D., Fellow, Center for Biomedical Ethics, Stanford University. “The goal for a long time has been the so-called ‘$1,000 genome,’ and there are signs that the field is approaching this. But that cost only covers the actual physical sequencing itself. So even if insurance companies agree to cover the cost of sequencing, it’s still not clear how many [additional] costs for interpretation they will agree to cover. And although the Genetic Information Non-Discrimination Act prevents insurance companies and employers from using genetic information as the basis for employment or coverage discrimination, it’s uncertain how [it’s] enforced.”
Watson agrees with Allyse that the interpretation of results is highly complex and very expensive—between $5,000 and $10,000—which will soon cost more than the sequencing itself.
But perhaps the most controversial issue is the disclosure of test results. In March, the ACMG released a report called “ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing,” which stated that incidental findings—those unrelated to the condition for which you’re tested—must be revealed to you. In short, the ACMG created a list of serious conditions and now recommends that the laboratory returns these incidental findings to your doctor who should manage the information with you. For example, if you undergo whole genome sequencing to help diagnose cardiovascular disease, but your test results also indicate a predisposition for cancer, your doctor has an obligation to tell you—even if you don’t want to know. The ACMG believes that revealing an incidental finding will help your doctor determine appropriate medical intervention that could possibly detect the cancer earlier and potentially save your life.
“It’s important to put the ACMG’s recommendations for reporting incidental findings into perspective,” says Watson. “The conditions on the list are relatively rare, and perhaps 1 percent of people without a known risk will be found to be at high risk for one of the conditions.”
Although the ACMG has good intentions, not everyone supports its recommendations on incidental findings. In response to the ACMG’s report, Allyse and Marsha Michie, Ph.D., Fellow, Center for Biomedical Ethics, Stanford University, co-authored a paper, “Not-so-incidental findings: the ACMG recommendations on the reporting of incidental findings in clinical whole genome and whole exome sequencing.” The paper, which was published in May in the journal Trends in Biotechnology, discusses their concerns with the ACMG’s recommendations.
“Our main objection [is] the way the ACMG’s recommendations fail to leave room for patients and their families to make their own decisions about which tests they want and which results they want to receive,” says Allyse. “While we support the right of patients and their families to have access to health information that they want, we think it’s wrong to force them to accept information they might not want.”
“[It’s] one of the big debates of our time,” adds Watson. “Do we only tell people what they want us to, or do we tell them that they’re about to be hit by a train they don’t see coming? I expect our challenge is to figure out where the lines are between.”
Indeed, knowing you have a predisposition for a serious disease can cause anxiety—especially since you may never actually develop the disease. But not knowing can be equally distressing. Either way, it’s a tough call. But since whole genome sequencing will most likely become the technology of choice for many laboratory tests in the near future, you should consider where you stand on this issue: whether you feel “ignorance is bliss” or “knowledge is power.”