CHEK2-Related Cancer Risk

The CHEK2 gene is classified as a “moderate risk” gene, meaning that there is a modestly increased risk for certain types of cancers.  Different genetic mutations in the CHEK2 gene may lead to different cancer risks. For example, women who have CHEK2 “truncating” or “frameshift” pathogenic gene mutations (the most common example being the CHEK2 “1100delC” mutation), have a relative risk of approximately 3 for breast cancer compared to the general population.  In comparison, women who have certain CHEK2 “missense” gene mutations are believed to have a lower risk for breast cancer.  An example of this lower cancer risk is with the CHEK2 “I157T” (also known as “Ile157Thr”) missense mutation is associated with a relative risk for female breast cancer of approximately 1.6 compared to the general population.  The risk for a woman to develop contralateral breast cancer (i.e. a second cancer diagnosis, but in the opposite breast) in the setting of a truncating CHEK2 gene mutation is believed to be increased.  CHEK2 gene mutations may also be linked to an increased risk for colorectal and prostate cancer, but the lifetime risks for these types of cancer are not yet clearly defined.  Further research is needed to understand the interactions of moderate risk genes and family history on lifetime cancer risk.


CHEK2 cancer screening and risk-reducing options

The best long-term medical management for individuals who carry a mutation in the CHEK2 gene is a topic of on-going research.  Healthcare providers oftentimes rely on an individual’s personal and family history to guide medical care.

  • Breast: Women who carry CHEK2 gene mutations should pursue standard clinical breast exams and annual mammography. Women who have clearly pathogenic CHEK2 gene mutations (e.g. CHEK2 1100delC) should additionally consider breast MRI starting at approximately 40 years of age, or earlier if there is a strong family history of breast cancer.  A genetic counselor or physician can advise if breast MRI is appropriate based upon the specific CHEK2 mutation present and personal and family histories.  For example, in the absence of a significant family history, the CHEK2 I157T mutation is not associated with a sufficient breast cancer risk to warrant breast MRI screening.
  • Colon: Depending upon personal and family history, women and men should undergo colonoscopy starting by age 45 years, or 10 years prior to the age of onset of the earliest colorectal cancer diagnosis in the family, and repeat this exam every 5 years.


CHEK2 associated therapeutic/ treatment implications

Individuals who have a cancer diagnosis and an identified CHEK2 pathogenic mutation should speak with their treating physician about the availability of targeted/ personalized treatment options.

Clinical trials evaluating different medications in individuals who have pathogenic mutations in CHEK2 and/or other related genes might be available now or in the future.


CHEK2 testing in other family members

At this point in time, testing adult family members for a moderate risk gene mutation does NOT provide the same clarity or guidance that testing for a high risk gene mutation does. This is because moderate risk gene mutations should not be assumed to be the sole explanation for a particular family’s history of cancer.  For example, a family could have additional unidentified genetic and/or non-genetic risk factors contributing to the development of cancer seen in family members.  It is recommended that family members discuss risks, benefits and limitations of genetic testing with their physician and/or genetic counselor.  If an adult family member were to test positive for the familial CHEK2 gene mutation, increased cancer screening might be considered.  However, given the current lack of data regarding CHEK2 gene mutations, if an adult family member were to test negative for a familial CHEK2 gene mutation, that individual may still be at increased risk for cancer depending upon the family history and possibility for other genes to be playing a role.  Cancer screening should be performed in accordance with the family history until further data is available.


Future considerations

As research and data on cancer risk estimates continue to evolve, physicians and researchers will gain a better understanding of how certain CHEK2 gene mutations influence medical care.  Because the information provided to patients will almost certainly change, those with a CHEK2 gene mutation are encouraged to keep in touch with their medical providers in order to receive updates.




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