The CHEK2 mutation is a variation in a gene that is associated with an elevated lifetime risk for developing several types of cancer. Individuals often discover this genetic change through commercial or clinical genetic testing, prompting questions about its long-term health implications and the possibility of passing it to their children.
The Role of the CHEK2 Gene
The CHEK2 gene (Checkpoint Kinase 2) is a tumor suppressor gene responsible for maintaining the stability of the cell’s genetic material. It provides the instructions for making a protein that acts as a sensor for DNA damage within the cell. When this sensor detects a break in the DNA strands, the CHEK2 protein becomes active and halts the cell division process.
This pause, known as cell cycle arrest, gives the cell time to repair the damage. If the DNA damage is too extensive to fix, the CHEK2 protein can signal the cell to self-destruct through a controlled process called apoptosis. A mutation in the CHEK2 gene compromises this surveillance system, allowing cells with unrepaired DNA damage to divide and potentially lead to the formation of a tumor.
How CHEK2 Mutations Are Passed Down
The CHEK2 mutation is hereditary, meaning it can be passed down from a parent to a child. This gene change follows an autosomal dominant inheritance pattern, which is the most common way single-gene disorders are transmitted. Autosomal means the gene is located on one of the non-sex chromosomes, and dominant means that a person only needs to inherit one copy of the mutated gene to have the cancer predisposition.
Each child of a person with a CHEK2 mutation has a 50% chance of inheriting the altered gene copy, regardless of the child’s sex. Inheriting the mutation increases the lifetime cancer risk, but it does not guarantee that a person will develop cancer.
Cancers Linked to CHEK2
An inherited CHEK2 mutation significantly increases the lifetime risk for female breast cancer. The risk for women with a CHEK2 mutation is estimated to be up to 30% or more, which is substantially higher than the general population’s lifetime risk of approximately 12.5%. The specific CHEK2 variant and an individual’s family history of cancer can influence this risk estimate.
Men also face an increased risk for breast cancer (which is rare in the general population) and an elevated risk for prostate cancer. For men with the mutation, the lifetime risk of developing prostate cancer is increased, with some studies suggesting the risk could be as high as 27%. The CHEK2 gene has also been linked to a potential increase in other cancers, including thyroid, kidney, and colorectal cancer. The exact lifetime risks for these other cancers are still being researched, and management is guided by personal or family history.
Steps After a Positive Test Result
The first step after receiving a positive result is a consultation with a genetic counselor. The counselor interprets the specific variant and integrates it with personal and family medical history to provide a risk assessment. They can also discuss reproductive options and address concerns about testing other family members.
Management includes enhanced cancer surveillance protocols that begin earlier than for the general population. For women, this involves beginning annual mammograms at age 40 and considering annual breast magnetic resonance imaging (MRI) with contrast starting between ages 30 and 35. Men with a CHEK2 mutation are advised to begin discussing prostate cancer screening, which may include a PSA test, with their doctor starting at age 40. Lifestyle adjustments, such as maintaining a healthy weight and avoiding smoking, are recommended to mitigate overall cancer risk.