A. Diagnostic testing
A diagnosis of a hereditary colorectal cancer syndrome, such as FAP, MAP, or lynch syndrome, is suspected based on personal and family history, or based on a tumor screening test. This diagnosis can often be confirmed or pinpointed with genetic testing. To make sure that the genetic cause is even detectable, genetic testing ideally starts with a member of the family who has cancer or polyps. This involves looking through an entire gene or several genes to pinpoint the genetic problem.
The first person in the family to have genetic testing will receive one of three results:
A Positive result means the underlying genetic cause (mutation) was identified. This confirms the specific diagnosis of the hereditary colorectal cancer syndrome in question. This clarifies your cancer risks, helps your doctors manage those risks, and allows for testing of family members.
A Negative result means that no underlying cause of a hereditary colorectal cancer syndrome can be pinpointed at this time. That is because of one of the following reasons:
1) The person with the negative test did not inherit the condition that runs in the family.
2) Colorectal cancer and polyps are common. Multiple diagnoses in the same family may simply be due to chance.
3) Some mutations are probably missed with today’s technology. As research and technologies improve, laboratories are sometimes able to identify mutations that were not previously found using older technologies.
4) The test didn’t look for the right genes. There are other genes that may increase the odds of colorectal cancer or polyps for which there is no testing at this time. Perhaps, testing for these other genes was not indicated by the personal or family history.
An Uncertain result occurs because some genetic testing can yield a “variant of uncertain significance (VUS).” A VUS is a genetic mutation that is different than usual, but it is unclear whether it actually causes a problem in the gene or not. It might be a rare, normal variation or it might be a problem for the gene, but it just isn’t obvious based on what is known today.
A VUS does not confirm or rule out a diagnosis. It should not be used for medical decisions. While family members should not use testing for a VUS to determine risk or recommendations, but may be asked to consider testing to help with research about the VUS. Often, as more research is done, the laboratories can determine if this genetic change is harmful or not. This can take months or years. Learn more from "Find My Variant."
Once a family member has a POSITIVE result, other family members can be tested for the same mutation. This is called “predictive testing.” One goal of predictive testing is to make sure people with the condition can get screening and/or surgeries in time to prevent cancers and/or detect cancers while curable. Another goal is to allow people who do not have the condition to avoid unnecessary screening, like colonoscopies. People who do not have the familial mutation are at the same risk as the general population to develop colorectal cancer and polyps.
The timing of predictive testing depends on when the condition typically starts to cause problems, which tells your doctors when to start cancer screening. For example, lynch syndrome causes adult onset cancers, and colonoscopies start around the ages of 20-25 years. Therefore, genetic testing is typically not offered until after the age of 18 years. On the other hand, children with FAP can begin developing polyps by their early to mid-teens, so colonoscopies begin around the age of 10-12 years. Therefore, genetic testing is typically offered around the age of 8-10 years.
Genetic Testing Types for Hereditary Colon Cancer Syndromes
B. Tumor Screening Tests for Lynch Syndrome
Two kinds of tests are commonly done on colon or endometrial cancer to look for signs of lynch syndrome. The tests are called microsatellite instability (MSI) and immunohistochemistry (IHC). These tests do not diagnose lynch syndrome, but do indicate whether additional testing for lynch syndrome may be useful. IHC tests whether the Lynch syndrome genes are showing up for work. The MSI looks to see whether they are actually doing their job.
For more information about these tests, visit the Lynch Syndrome Screening Network’s website.
C. Pre-implantation testing
Pre-implantation testing is a technique that uses genetic testing, along with in-vitro fertilization (IVF) to select and transfer embryos that do not have the genetic condition. This technique is also called pre-implantation genetic diagnosis (PGD). If a mutation has been identified in the family, this process can be used to reduce the odds of having a child with a particular genetic condition, such as FAP, AFAP, MAP, or lynch syndrome.
This technology is very good, but does not work 100% of the time. PGD can never guarantee that you will not have a child with a hereditary colorectal cancer syndrome. This testing can be expensive and may not be covered by insurance plans companies.
D. Other Prenatal Testing
Genetic testing can also be done during pregnancy to determine whether the condition is present or not.
1) What are the benefits and risks of genetic testing?
2) How does genetic testing work?
3) What is the cost of genetic testing?
4) What have others experienced with genetic testing?
Development of this resource was generously supported by Myriad Genetics.