Genetic Insights: quick reference guide for healthcare providers
This guide is intended to facilitate a discussion between a provider and their patient.
Genetic Insights test results: CHEK2-associated hereditary cancer
Contents
Key results
A variant called c.470T>C (p.Ile157Thr) was found in the CHEK2 gene.
People with this DNA variant in the CHEK2 gene have a slightly increased risk of breast cancer in females, prostate cancer in males, and colon cancer in both.
Next steps
| Clinical recommendations | Resources |
| Genetic Insights is a screening test and is not intended for diagnosis. A follow-up genetic test should be performed in a clinical setting before any other action is taken. | Ready to order? Check with your institution and/or patient’s insurance about the preferred testing laboratory. Blueprint Genetics® offers hereditary cancer testing. To confirm this test result, targeted variant testing for the variant identified is available. You can order a confirmation test here: Blueprint Genetics/TVT Have questions? Call 1.866.GENE.INFO (1.866.436.3463) to speak to a specialized Quest genetic counselor or geneticist available to healthcare providers to discuss test selection and results. |
| Refer your patient to a genetic counselor specializing in hereditary cancer. | Your patient can schedule a 1-on-1 remote genetic counseling session through their online Genetic Insights Cancer Risk Report at no additional cost. |
| Genetic counselors can provide counseling on the implications of this test result and next steps for your patient. | To find a genetic counselor with expertise in hereditary cancer practicing in your patient’s area for an in-person session, please visit FindAGeneticCounselor.NSGC.org |
Patient conversation starters:
Patient conversation starters summarize the preceding information in plain language to support meaningful conversations between you and your patient.
FindAGeneticCounselor.NSGC.org
Your Genetic Insights test is a screening test. The next step is to have your result confirmed with a second genetic test.
It’s also important that you talk with a genetic counselor. Genetic counselors are experts in genetics and can help you understand this result and potential next steps.
You can access a genetic counselor through your online Genetic Insights dashboard at no additional cost to you, and we can discuss a referral to a local genetic counselor.
What is CHEK2-associated hereditary cancer?
DNA variants in the CHEK2 gene are associated with a higher lifetime risk of certain cancers, often with an earlier age of onset than the general population.1,2
However, cancer risks may vary based on family history, the specific DNA variant identified, and other factors.
People with a confirmed CHEK2 DNA variant are recommended to undergo more frequent cancer screening, typically starting at earlier ages than in the general population.2
See the Management options section for more detail.
What this result means for family members
Family members may have the same DNA variant. The DNA variant was most likely inherited from a parent. Full siblings and children have a 50% chance of having this variant.
In people with a confirmed DNA variant in the CHEK2 gene, cascade genetic testing for other family members 18 years and older may help inform their risks and screening protocols.
A genetic counselor can help determine the most appropriate testing options. Therefore, it is strongly recommended that people share their results with their biological relatives.
Patient conversation starters:
Your test showed a specific DNA variant in the CHEK2 gene.
People with this variant have a higher chance of developing certain types of cancer in their lifetime.
Not everyone with this variant develops cancer. The type of cancer and the risk of cancer can vary based on personal or family health history and the specific DNA variant in the CHEK2 gene.
People with a DNA variant in the CHEK2 gene usually have screenings earlier in life and more often than typical. This increases the chance that if cancer develops, it’s detected as early as possible.
Patient conversation starters:
DNA variants in the CHEK2 gene run in families. That means the DNA variants can be inherited or passed down from parents to their children.
Your close relatives, like your parents, full siblings, and children, have a 50% (or 1 in 2) chance of having the same DNA variant. Other relatives might also have the same DNA variant.
Sharing this result with your family members is important so that they can talk to a healthcare provider about genetic testing for CHEK2 DNA variants.
Cancer risk
Select cancer risks in people with a confirmed c.470T>C (p.Ile157Thr) variant in the CHEK2 gene are listed below. However, research is ongoing to better understand the cancer types linked to the c.470T>C (p.Ile157Thr) variant in the CHEK2 gene and the associated risks. Therefore, this risk information may change over time.
| Cancer type | Approximate lifetime risk in people with the c.470T>C (p.Ile157Thr) CHEK2 variant | Approximate lifetime risk in the general population |
| Assigned female at birth: | ||
| Breast | Up to 21%1 | 13%4 |
| Assigned male at birth: | ||
| Prostate | Up to 22%7 | 12.1%6 |
| Males and females: | ||
| Colon | Up to 7%1 | 4%5 |
Management options
There are options for cancer risk management for people with a DNA variant in the CHEK2 gene. Clinical guidelines from the National Comprehensive Cancer Network® (NCCN®) for people with a confirmed CHEK2 DNA variant and no personal history of an associated cancer are listed below.2,3
However, screening and management should consider the variable cancer risks depending on the specific CHEK2 variant identified. 2,3
The risks associated with the CHEK2 c.470T>C (p.Ile157Thr) DNA variant may not meet a threshold for management change from typical. 2,3
| Cancer type | Guidelines for people with CHEK2 DNA variant |
| Breast (assigned female at birth) |
Annual mammogram starting at age 40 (or earlier based on family history) Consider breast MRI with contrast starting at age 30-35 (or earlier based on family history Discuss option of risk-reducing options based on family history |
| Colon | For individuals with a first-degree relative with colorectal cancer, colonoscopy screening every 5 years, beginning at age 40 or 10 years prior to age of first-degree relative’s age at colorectal cancer diagnosis, whichever is earlier For individuals with no known family history of colorectal cancer, colonoscopy screening every 5 years beginning at age 40 |
| Prostate | No recommended changes to standard cancer screening at this time |
Patient conversation starters:
People with the CHEK2 c.470T>C (p.Ile157Thr) DNA variant may need to consider additional cancer screening beyond what is typical. If your test result is confirmed, it is important to work with the right specialists—like a medical oncologist and a geneticist—to find cancer screening options that are right for you.
See NCCN for complete recommendations. Recommendations may change over time.
If the test result is confirmed, local centers for excellence in hereditary cancer should be consulted for further clinical management
Additional resources
The following patient advocacy groups have additional information and resources about CHEK2-associated hereditary cancer:
Facing Our Risk of Cancer Empowered (FORCE): FacingOurRisk.org
References
- Han FF, Guo CL, Liu LH. The effect of CHEK2 variant I157T on cancer susceptibility: evidence from a meta-analysis. DNA Cell Biol. 2013 Jun;32(6):329-335. doi:10.1089/dna.2013.1970
- National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic (Version 1.2023). Accessed December 15, 2022. www.nccn.org
- National Comprehensive Cancer Network®. Genetic/Familial High-Risk Assessment: Colorectal (Version 2.2022). NCCN Guidelines®. Accessed December 15, 2022
- National Cancer Institute. Cancer Stat Facts: Female Breast Cancer. Accessed December 15, 2022. https://seer.cancer.gov/statfacts/html/breast.html
- Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Colorectal Cancer. Accessed December 15, 2022. https://seer.cancer.gov/statfacts/html/colorect.html
- National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Prostate Cancer. Accessed December 15, 2022. https://seer.cancer.gov/statfacts/html/prost.html
- Wang Y, Dai B, Ye D. CHEK2 mutation and risk of prostate cancer: a systematic review and meta-analysis. Int J Clin Exp Med. 2015;8(9):15708-15715. https://www.ncbi.nlm.nih.gov/pubmed/26629066
This information is not a substitute for medical advice, diagnosis, or treatment. The diagnosis or treatment of any disease or condition may be based on personal history, family history, symptoms, a physical examination, laboratory test results, and other information considered important by a healthcare provider.
Individuals should talk with a healthcare provider about the meaning of genetic test results and before stopping, starting, or changing any medication or treatment.
Genetic Insights is a test developed and performed by Quest Diagnostics. The test results are not diagnostic and do not determine overall chances of developing a disease or health condition. The tests are not cleared or approved by the US Food and Drug Administration.
QuestDiagnostics.com
Quest, Quest Diagnostics, any associated logos, and all associated Quest Diagnostics registered or unregistered trademarks are the property of Quest Diagnostics.
All third-party marks—® and ™—are the property of their respective owners. © 2023 Quest Diagnostics Incorporated. All rights reserved. MI12000 3/2023