CHEK2-associated hereditary cancer

What Does It Mean to Test Positive for a CHEK2 Mutation?

Individuals who test positive for a mutation in the CHEK2 gene have a moderately increased risk of developing cancer over their lifetime. The risk of developing cancer can be influenced by family history as well as the specific CHEK2 mutation identified. Most mutations in CHEK2 are associated with a moderately increased risk of female breast cancer. CHEK2 mutations may also influence the risk of male breast, colon, and prostate cancers. However, it is important to understand that the risk of cancer is not 100%, which means that not everybody with a CHEK2 mutation will develop cancer.

What Are the Cancer Risks Associated with a CHEK2 Mutation?

Cancer risks for men and women who have a mutation in CHEK2 are influenced by family history and the specific mutation identified. A thorough family history review is important to better understand cancer risks and to develop an individualized cancer screening plan with a healthcare provider.

In general, women identified to have a mutation in CHEK2 have an estimated lifetime breast cancer risk of 20 to 25%, compared to the general population's risk of 12%. This risk may be higher in some individuals who have a family history of breast cancer, as outlined in the table below:

Family History of Breast Cancer Estimated Lifetime Female Breast Cancer Risk
No Family History 20 to 25%
One First-Degree Relative 34%
One Second-Degree Relative 28%
On First and One Second-Degree Relative 44%

Data adapted from Cybulski et al. (2011). This study is limited to patients of European descent and may not reflect the risk in other ethnicities.

Mutations in CHEK2 may also be associated with a lifetime colon cancer risk of 8 to 15%, compared to a 4% risk for colon cancer among individuals who do not have a CHEK2 mutation. As with the risk of breast cancer, the risk of colon cancer may be higher in individuals who have a family history of colon cancer.

Cancer Type Cancer Risk Average Age of Onset General Population Risk
Breast 20 to 44% Unknown 12.4%
Second Primary Breast Cancer 29% within 10 Years of First Diagnosis Not Applicable 4 to 9% within 10 Years of First Diagnosis
Colon 8 to 15% Unknown 4.3%

Mutations in CHEK2 have been reported with many other types of cancer, such as prostate cancer. However, more research is needed to determine the additional cancer types and possible associated risks.

What Cancer-Screening or Risk-Reducing Options Are Available?

The most important aspect of management of an individual with a CHEK2 mutation is increased cancer screening, to allow the earliest possible detection of any tumors.

Specific management guidelines for CHEK2 mutations are evolving and are often individualized based on family history. Current recommendations include:

For Women

  • Clinical breast examination is recommended every 6 to 12 months.
  • Mammography, with consideration of 3D mammogram (tomosynthesis) and breast MRI, is recommended once a year beginning at age 40 or earlier, depending on family history.
  • Additional risk-reduction strategies, such as prophylactic mastectomy (surgical removal of both breasts) or the use of medication, may also be considered on an individualized basis, but are not routinely recommended at this time.

For Men and Women

  • Colonoscopy is recommended every five years, beginning at age 40 or 10 years earlier than the earliest age of colon cancer diagnosis in a first-degree relative.

What Is the Chance That Family Members of CHEK2 Mutation Carriers Have the Same Mutation?

CHEK2 mutations are passed down in a family. This means that family members of CHEK2 mutation carriers may have the same mutation and may also be at increased risk of developing cancer. For this reason, it is important for CHEK2 mutation carriers to discuss genetic test results with family members.

  • Close blood relatives of CHEK2 mutation carriers, such as parents, siblings, and children, have a 50% chance of having the same mutation.
  • Distant relatives, such as aunts, uncles, grandparents, and cousins, also have a chance of having the same CHEK2 mutation.
  • A physician or a genetic counselor can help mutation carriers determine whether the mutation was more likely to have been inherited from the maternal or paternal side of the family. In general, the mutation will only be found on one side of the family, and it is more likely to be on the side of the family that has a history of breast cancer.

Genetic testing of family members can help determine which family members may have an increased risk for cancer and may benefit from screening and/or risk reduction options discussed above. Because CHEK2 mutations do not always explain all of the cancer risks in a family, family members who test negative for a known familial CHEK2 mutation may still be at increased risk for cancer, based on their family history.

What Else Should CHEK2 Mutation Carriers Know?

Mutation carriers who are interested in options to prevent passing their mutation to future children may wish to consider preimplantation genetic diagnosis (PGD). PGD is a procedure that involves in vitro fertilization (IVF) and can determine if an embryo carries the genetic mutation present in a family. Determining which embryos carry the family mutation may allow a mutation carrier to prevent the condition from being passed to future children. The decision to undergo PGD is personal. Mutation carriers and their family members can talk with a healthcare provider to learn more about their reproductive options.