February 28, 2002
Genetic information and patient care
| Walter Neary |
| HS News & Community Relations From Boston |
Genetic sciences provide key insights into many health-care conditions — but the more scientists learn, the more they need to know, says Dr. Wylie Burke, professor and chair of the Department of Medical History and Ethics in the UW School of Medicine.
Burke addressed a panel here last week at the annual meeting of the American Association for the Advancement of Science. The panel, “The Present State of Genomic Medicine,” discussed how the basic science of genetics has proven useful in the diagnosis and treatment of patients.
The panel was organized by Drs. Jeffrey Drazen, editor of the New England Journal of Medicine, and Francis Collins, director of the National Center for Human Genome Research, National Institutes of Health. It served as a followup to last year’s presentations at AAAS on genetics, which tended to focus on the then-recently announced publication of the Human Genome Project sequencing.
Burke’s portion of the program was titled “Genomics as Guide to Disease Classification, Prognosis and Pathophysiology.” She provided the audience with several examples that illustrate the complexity of using genetics with medicine.
There are some conditions that are quite straightforward, where the genetic mutation appears to trump all other factors. For example, Duchenne muscular dystrophy is caused by deletion of a certain gene sequence in the dystrophin gene. The deletion causes the fatal condition because dystrophin is an important protein needed for muscle function.
Building on that discovery, scientists have found two other disorders caused by mutations in the dystrophin gene: Becker’s muscular dystrophy, which tends to strike later in life, and X-linked cardiomyopathy, where the loss of dystrophin is primarily in cardiac muscle.
However, genetic risk is only part of the story for many conditions. Burke, who sees patients with genetic conditions at UW Medical Center, says that many genetic diseases appear to be modified by other factors that are still unknown. For example, consider perhaps the best-known genetic mutations, BRCA 1 and BRCA 2, which are linked to breast cancer. Burke noted that in published studies, women with a particular form of the mutation — 185delAG — share a predisposition to cancer, but may have very different family histories and experiences with the disease:
One woman suffered ovarian cancer when she was 58 but there was no evidence of cancer in her daughter, or in her own mother.
Another woman with the identical mutation had breast cancer when she was 73 and her niece came down with breast cancer when she was 45.
Yet another woman with the same mutation came down with breast cancer in her 30s and ovarian cancer in her 40s, while her mother only had breast cancer and her daughter suffered breast cancer in her 30s and ovarian cancer in her 40s.
While they and their families have different histories, each of these women has the same mutation. “When you try to relate genetics to a the clinical picture, it becomes a very complex story,” Burke said. “It appears to be the rule, rather than the exception, that genes are modified by other genes and by effects in the environment.” For BRCA 1 and 2 research, the next important step will be to identify how the cancer risk is modified. This could lead to new insights about prevention.
And it appears that complexity is the rule in general. Consider the case of hemochromatosis. This condition, shorted to HHC, is associated with excess iron accumulation. That leads to iron overload within the body, and conditions such as cirrhosis, diabetes, arthritis and heart failure. There are three mutations linked to the condition, which all have names like the code for car parts: C282Y, H63D and S65C.
Environmental factors or other genetic factors play a role in this condition as well. Burke cited a study describing two families with the C282Y mutation: in both, two of the siblings had the iron disorder, but a third sibling did not. Yet all had the known genetic risk. Researchers do not know why some people with the genetic predisposition develop disease, and others do not.
“While our knowledge can grow only incrementally, genetic science has much promise for the future,” Burke says. “In the short term, genomics will help us to identify people most at risk, giving us the opportunity to help them with intensified preventive efforts. In the long term, however, genomics is likely to make even greater contributions as a tool for analyzing the biological pathways of illness. This could lead to better treatment for everyone.”
