In terms of heart disease, physicians often employ risk-prediction models, which use cholesterol, blood pressure, and other measures to predict an individual’s risk of developing heart disease over the next decade and to individualize treatments. Patients classified as high risk may be prescribed an aggressive cholesterol-lowering drug regimen or be told to reduce their lipid levels to a lower target than those in a lower risk group. But studies examining whether incorporating a heart-disease-linked variant on chromosome 9 (9p21, which is used in the Decode heart test) into standard prediction models have had mixed results. “It’s not yet clear that the 9p21 variants by themselves will provide a sufficiently large increment in knowledge about risk to dramatically change how we categorize people with respect to risk,” says Herrington.
The different outcomes for 9p21 may be tied to different populations under study, emphasizing the need to identify who might benefit from such tests. “At the individual level–not the population level–the genomic markers may be quite helpful,” says Eric Topol, director of the Scripps Translational Science Institute in La Jolla, CA. “Even [reclassifying someone] from no risk to moderate risk is an important point for an individual and his or her physician to be aware of.” One case in which Topol says that specific genetic testing may be useful is for patients who have had a stroke of unknown cause: they may consider being tested for the genetic variant linked to atrial fibrillation, an abnormal heart rhythm that can increase risk of stroke.
Scientists are now starting to test whether combinations of risk factors may have a larger effect on risk prediction. In the case of breast cancer, several common genetic risk factors have already been identified. The Decode cancer test identifies eight such variants. According to Stefansson, women who carry two copies of all eight have a 50 percent risk of developing breast cancer over their lifetime.
“The National Cancer Institute recommends that women with a 20 percent or greater lifetime risk of breast cancer should have an annual image of the breast,” says Stefansson. “This is an indirect way of saying it’s important to identify women with a 20 percent or more risk.”
But others say that it’s not yet clear how to combine knowledge of multiple genetic risk factors. “We don’t yet know how to combine such data in an accurate way,” says Evans. Accurate estimates are especially important for patients who might choose radical prevention measures, namely mastectomy, he says.
“Such information is not now and may not ever be ready to use in a direct clinical manner, but that does not mean that it isn’t incredibly important information,” says Evans. “These kinds of data will tell us lots about the origins of cancer, will increase our understanding of the disease, and will surely have long-term beneficial impact on drug design and treatment.”