For many years, patients seeking genetic testing concerning personal and/or family histories of cancer were offered testing for high-risk and well-understood genes. It has been long known that additional genes contribute to increased risks for cancer, but clinical testing for many of these genes was not readily available, affordable or time-efficient until just a few years ago. The advent of multi-gene cancer panel testing has dramatically altered the landscape of cancer genetics. Cancer panels now allow patients to be tested for genes beyond just the high-risk and well-established culprits. While these tests allow patients to broaden the scope of their testing, not all genes included on cancer panels are created equal. Many of the genes currently available are considered “moderate-risk” or “low-risk or newly discovered” genes. While finding a genetic change in any gene may provide insight into the concerning cancer history, it is important to speak with a genetics professional to consider the value this information may or may not offer as well as the possible limitations and drawbacks to cancer panel testing.
What are moderate and low-risk genes? Moderate risk genes are considered to be fairly well studied genes that are associated with more modest increases in cancer risk. For example, most mutations in a gene called CHEK2 lead to a ~20-25% lifetime risk for female breast cancer. By comparison, mutations in the BRCA1/2 genes increase lifetime breast cancer risk to ~40-60%. Low risk or more newly discovered genes are even less well understood and in most cases, the types of cancer risks related to these genes and lifetime risk estimates are unknown or ill defined.
One argument for cancer panel genetic testing is that identifying a harmful mutation in a moderate or low-risk gene may provide additional insight into the underlying genetic cause for an individual’s history. This result may alert an individual to an increased risk for cancer that would not have been apparent based on family history alone. Screening and management guidelines are available for some moderate risk genes, however these guidelines are limited in scope and continue to evolve alongside our understanding about risks associated with these genes.
In the event that an individual is found to carry a harmful mutation in a moderate or low-risk gene, it is important to be aware that this mutation alone may not provide an explanation for the concerning history. Given that mutations in these genes influence cancer risk to a lesser degree than their high-risk counterparts, it is likely that they serve as a piece of the patient’s larger risk puzzle, but are not the sole driver of their cancer risk. Given this, individuals in this scenario are encouraged to report changes to their personal and/or family histories and possibly reconsider additional genetic testing in the future in an effort to uncover additional puzzle pieces.
On an individual level, it is important to weigh the value of the information these genes may provide against the potential for added complexity and increased anxiety. Considering the pros, cons and limitations of multi-gene cancer panel testing and discussing these with a genetics provider is an important step in determining if cancer panel testing is appropriate for you.