Studies advance integration of genetics with medical care
We’ve known for a long time that certain families appear to have a risk for colon cancer. The way we’ve evaluated the risk for Lynch syndrome-associated cancers so far has mostly depended upon a certain set of strict criteria: There have to be three cases of colon or other related cancers in two generations of the family and one of the cases has to be diagnosed before the patient is 50 years old.
“The [new] models are primarily tools to help physicians decide whether to order a genetic test based on the clinical data available to them.”
The problem is, not all Lynch syndrome families have that exact pattern, so a fair number of people are going to be missed. These new prediction models are designed to catch some of those other cases.
How tests may be used
What the PREMM1,2 and the MMPro do is predict the likelihood that, if you do a genetic test on a person believed to be at risk, it will show that they have a mutation in the MLH1 or MSH2 genes. The models are primarily tools to help physicians decide whether to order a genetic test based on the clinical data available to them.
Any mutation prediction model is going to be complicated because in order to be accurate, you take into account lots of variables. The good thing about the original criteria is that they weren’t very complex.
These new prediction models are an attempt to formalize what genetic specialists have been doing for years. However, I don’t think most doctors will use them, although specialists such as gastrointestinal oncologists may. These models will probably be most useful for genetic counselors and for providing doctors with a better idea of what types of family history and clinical factors are useful in evaluating cancer risk.
Importance of determining hereditary cancer
When colon cancer is associated with Lynch syndrome, there is a 50 percent increase in the chances of a new colon cancer developing. People with this syndrome will need to be tested annually, as will members of their immediate family. Lynch syndrome also puts a person at greater risk for other cancers—including upper gastrointestinal, urinary, endometrial and ovarian cancers.
“Colonoscopy in families with Lynch syndrome reduces the incidence of colon cancer by 50 to 75 percent.”
Lynch syndrome-related colon cancers tend to occur as early as the age of 20 to 25, so screening should start at an earlier age. In the general population, screening with a colonoscopy or sigmoidoscopy is recommended beginning at age 50.
Information about genetic mutations is very important in making surgical decisions. The surgeon may decide, for example, to remove the entire colon because of the high risk of a second colon cancer developing later.
Genetic counseling and testing
Understanding these hereditary cancers is just the first step in integrating genetics into medical care. As we do more research, we hope to get a better idea of how to prevent many types of cancer and other diseases based on a genetic profile.
We already know, for example, that colonoscopy in families with Lynch syndrome reduces the incidence of colon cancer by 50 to 75 percent. When the colonoscopy is performed, colorectal adenomas or polyps that turn into cancer can simply be removed. If cancers do develop, they tend not to be as advanced.
Estimates are that 5 to 10 percent of all cancers are hereditary. For some, like prostate or lung cancers, there are no genetic tests currently available. The most common tests are for colon, breast and ovarian cancers.
Genetic tests are most appropriate when there is a strong chance the patient has a mutation, the presence of a mutation will change the clinical management, and intervention is available that will impact the risk for cancer. For example, promising data shows that taking tamoxifen will reduce by 50 percent the chances for developing breast cancer even in women carrying a genetic mutation that puts them at risk.
Insurance often pays for all or part of these tests if the possibility of identifying a genetic mutation is high and the patient’s medical management will be significantly affected. The test itself involves taking a small blood sample. Results are usually available in four weeks.
If a person is trying to decide whether to pursue genetic counseling and testing, it’s a good idea to make a family medical history and show it to the family doctor. A good online tool for making your family tree can be found at www.nsgc.org. Another option is to call a genetic counseling program such as the program at UK Markey Cancer Center for more information.
Heather Pierce is director of the Clinical Genetic Counseling Program at UK Markey Cancer Center and assistant professor of hematology and oncology in the UK College of Medicine.