At a glance
Also known as
Lynch syndrome (MLH1; MSH2; MSH6; PMS2; EPCAM); Familial adenomatous polyposis (APC); MUTYH-associated polyposis (MUTYH); Juvenile polyposis syndrome (SMAD4; BMPR1A); Peutz-Jeghers syndrome (STK11); Hereditary mixed polyposis syndrome (GREM1).
Why get tested?
To assess the risk of developing colorectal cancer (cancer of the large intestine or rectum), endometrial cancer (cancer of the lining of the uterus or womb), or other cancers associated with heritable genetic changes.
If an individual is identified as being at high risk of developing certain cancers, treatment options can be considered to reduce this risk.
When to get tested?
Genetic testing may be offered by a specialist or consultant physician for a person with features that are suggestive of a heritable familial colorectal cancer syndrome.
Genetic testing of an unaffected person is generally not performed unless a specific genetic fault (pathogenic variant) has already been identified in a family member.
Genetic testing of unaffected family members is offered only through a family cancer clinic. If an individual is referred to a family cancer clinic, the potential benefits, limitations, and possible consequences of genetic testing will be discussed prior to deciding whether to proceed.
A blood sample drawn from a vein in the arm.
How is it used?
Thousands of different disease-causing changes have been reported in genes associated with colorectal, endometrial and other cancers. An affected person is tested first to determine whether their features are due to a fault in a gene associated with familial cancer and, if so, what their particular genetic fault (variant) is. This is known as “diagnostic testing”.
Once a “familial variant” has been identified, other family members can then be tested for that specific variant to determine their personal cancer risk. This is known as “predictive (or pre-symptomatic) testing”, and is only offered through a family cancer clinic. Predictive (pre-symptomatic) testing is helpful in deciding whether to take additional measures such as regular surveillance (screening) or prophylactic surgery that may reduce the chance of developing certain cancers in the future.
What does the test result mean?
If a positive result is obtained (i.e. a disease-causing genetic variant is detected), a genetic counsellor will explain the meaning of the result and the steps which can be taken to reduce the chance of developing certain cancers in the future. These risk-reducing interventions are tailored specifically to the disease pattern of each cancer syndrome, and take into account the tested individual’s personal and family history. Risk-reducing measures may include options of regular surveillance (screening), prophylactic surgery or risk-reducing medication.
A negative result does not mean that the person will not develop colorectal or other cancers. It simply means that the individual is not at increased risk for developing cancer related to the genetic variant for which he/she was tested. It should be remembered that most cases of colorectal and endometrial cancers are not caused by a heritable familial cancer syndrome.
A negative result in an affected individual may also mean that the person has a genetic variant which is not detectable by the test method used, or that the person has a variant in a different (perhaps undiscovered) gene. For negative results, a genetic counsellor or specialist will provide tailored advice based on the individual’s personal and family history.
Is there anything else I should know?
There are many issues to be considered when preparing for a genetic test and after learning the result. Pre- and post-test consultation with a genetic counsellor or specialist is a vital step in the testing process. The potential benefits, limitations, and possible consequences of genetic testing will be discussed prior to deciding whether to proceed.
Positive genetic test results often have implications for other family members. When one family member is found to have a disease-causing variant, concerns may arise about how or whether to share this information with other family members. Genetic counsellors can provide advice about communication of results with other family members.
Sometimes, a genetic change may be identified but the laboratory is unable to determine whether the change may cause disease. This is known as a “variant of uncertain significance”. A genetic counsellor or specialist will provide further advice, taking into consideration the individual’s personal and family history. Further information may become available in the future as scientific knowledge advances.