In this blog post we will walk you through the various possible outcomes of your GeneMate® test (see figure).
A positive result means that a pathogenic variant was identified in one of the 41 genes that were analyzed. All genetic variants that are identified with GeneMate® are inherited in an autosomal dominant manner (with the exception of variants in the MUTYH gene which are inherited in an autosomal recessive manner). This means that a pathogenic variant in one copy of the affected gene is enough to give a moderate to high risk of cancer (monogenic disorder).
Those with a positive result can expect a comprehensive report with information about the varied gene and next steps. The customer is also encouraged to book an appointment for genetic counseling, during which they may opt for referral to the health care system for inclusion in screening programs and carrier testing for relatives. Genetic counseling also gives a valuable opportunity to ask questions about your result and discuss potential concerns. Carrier testing is the testing of family members for the specific variant that was found in the initially tested individual. Family members who do not carry the variant will not have an increased risk of cancer. Family members who are carriers will get access to screening programs.
Most individuals that take the GeneMate® test will receive a negative result. This is because inherited variants associated with hereditary cancer risk are rare in the general population. A negative result, however, does not automatically exclude an increased risk of cancer. There exist genes that contribute to increased risk for cancer outside of those that are included in today’s clinical genetic testing (this includes GeneMate®). One variant in these genes alone does not contribute to disease, but rather a combination of variants in several different genes contributes to increased risk of cancer (polygenic disease). There is no clinical testing that tests for a combination of genetic variants to date. Instead, an individual’s family cancer history can be used to calculate cancer risk. Individuals with an increased risk of cancer based on their family history* may therefore qualify for screening programs, even in the absence of a pathogenic variant in the family.
As a result, customers with a negative GeneMate® test result but with a family history that is associated with hereditary cancer, may be recommended further evaluation of their hereditary risk within the health care system. The reasons for this are:
The health care system can verify family cancer history by accessing hospital records or the cancer registry, which the iCellate team cannot. This helps validate the risk assessment and assign individuals to the right screening program.
It may be important to test someone else in the family. A negative GeneMate® test indicates that the customer does not carry a pathogenic variant, but it does not confirm carrier status for other family members (as the risk of inheriting a pathogenic variant is 50%). Therefore, it may be relevant to test a family member that has or has had cancer. If this person also tests negative it is less likely that the cancer in the family is caused by a pathogenic variant and more likely to be polygenic (meaning that all family members have about the same cancer risk). However, if the family member tests positive for a pathogenic variant it is most likely the cause of the cancer in a family (monogenic). It that case only carriers will have an increased risk of cancer and non-carriers will have an average risk.
For customers that lack a family cancer history* associated with hereditary cancer, and have a negative result, the risk of cancer is the same as for the general population. Even those who test negative should take part in national cancer screening programs intended for the general population.
*A family history of cancer means that there is a combination of different cancer types in a family, such as breast, ovarian, prostate, and/or pancreatic cancer.
Anna Hellquist, Genetic Counselor at iCellate Medical AB, PhD Cell and Microbiology