CHEK2 Biallelic gene

Associated Syndrome Name: CHEK2-associated Cancer Risk (biallelic)

CHEK2 Biallelic Summary Cancer Risk Table

Cancer Genetic Cancer Risk
BreastHigh Risk
ColorectalElevated Risk
Male BreastElevated Risk

CHEK2 Biallelic gene Overview

CHEK2-associated Cancer Risk (biallelic) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13
  • Women with biallelic CHEK2 mutations have a risk for breast cancer that is significantly increased over the 12.5% lifetime risk for women in the general population of the United States. This risk is also significantly higher than the breast cancer risk for women with a mutation in only one copy of the CHEK2 gene (monoallelic mutation).
  • Men with CHEK2 mutations also have an increased risk for breast cancer. The estimates provided in the following table are based on studies of men with a single CHEK2 mutation. The risks for men with biallelic CHEK2 mutations may be higher.
  • Individuals with CHEK2 mutations may have an elevated risk for colorectal cancer, and the National Comprehensive Cancer Network (NCCN) has provided screening recommendations to address this possible risk.
  • It is not known if there are additional cancer risks for men and women with mutations in both copies of the CHEK2 gene. Some studies have described a possible increased risk for a wide range of cancers in patients with a single CHEK2 mutation, including prostate, gastric, thyroid, hematological malignancies, testicular germ cell tumors, and other malignancies. However, these studies are not conclusive and there are currently no medical management guidelines to address these possible risks.
  • Although there are increased risks for cancer in men and women with mutations in CHEK2, there are interventions that may reduce these risks. Guidelines from the National Comprehensive Cancer Network (NCCN) that may apply are listed below. These guidelines were developed for men and women with a mutation in only one copy of the CHEK2 gene. It may be appropriate to modify these recommendations based on the possibility of higher cancer risks in patients with mutations in both copies of the CHEK2 gene. Since information about the cancer risks associated with biallelic CHEK2 mutations is relatively new, and there is still some uncertainty about the best ways to reduce these risks, it may be appropriate to interpret these results in consultation with cancer genetics experts in this emerging area of knowledge.

CHEK2 Biallelic gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
Female BreastTo age 801, 14Up to 89%10.6%
Second primary within 10 years of first breast cancer diagnosis12, 15Up to 29%, or higher4.0%
Male BreastTo age 809, 140.4%-1%, or higher<0.1%
ColorectalTo age 806, 14Possibly elevated risk2.8%

CHEK2 Biallelic Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
Female BreastThe recommendations below were developed for women with a single CHEK2 mutation. Currently there are no specific management recommendations for breast cancer risk in women with biallelic CHEK2 mutations. However, the increased risk for breast cancer in biallelic carriers compared to monoallelic carriers warrants consideration of more aggressive management, such as starting screening at younger ages, performing screenings more frequently, and additional risk-reduction strategies.17NANA
Breast awareness - Women should be familiar with their breasts and promptly report changes to their healthcare provider. Periodic, consistent breast self-examination (BSE) may facilitate breast awareness.16IndividualizedNA
Clinical encounter, including clinical breast exam, ongoing risk assessment and risk-reduction counseling16When genetic risk is identified, but not before age 21Every 6 to 12 months
Mammography with consideration of tomosynthesis and consideration of breast MRI with contrast17Age 40, or modified to a younger age based on the family history of breast cancerAnnually
Consider additional risk-reduction strategies.16, 17IndividualizedNA
Male BreastCurrently there are no specific medical management guidelines for male breast cancer risk in mutation carriers. However, the increase in risk warrants consideration of options for male breast cancer screening, such as patient breast awareness education and clinical breast examinations.16, 17IndividualizedNA
ColorectalColonoscopy640 years, or 10 years younger than the age of diagnosis for any first-degree relative with colorectal cancerEvery 5 years

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the CHEK2 Biallelic gene.

This patient's relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females and males who have this/these mutation(s) are provided below.

Family members should talk to a healthcare provider about genetic testing. Close relatives such as parents, children, brothers and sisters have the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, and grandparents also have a chance of carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the same mutation(s) who may benefit from surveillance and early intervention.

Since this patient has mutations in both copies of the CHEK2 gene, it is almost certain that each of their parents and all of their children carry a CHEK2 mutation. Brothers and sisters are at very high risk for carrying either one or two CHEK2 mutations. Since even a single CHEK2 mutation can lead to a significantly increased risk for cancer, it is especially important that this information be shared within the family and relatives talk with a healthcare provider about testing.

The children of this patient are at risk of inheriting two CHEK2 mutations only if the other parent is also a carrier of a CHEK2 mutation. Screening the other biological parent of any children for CHEK2 mutations may be appropriate.


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  2. Weischer M, et al. CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer. J Clin Oncol. 2012 30:4308-16. PMID: 23109706.
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  8. CHEK2 Breast Cancer Case-Control Consortium. CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet. 2004 74:1175-82. PMID: 15122511.
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  10. Cybulski C, et al. A large germline deletion in the CHEK2 kinase gene is associated with an increased risk of prostate cancer. J Med Genet. 2006 43:863-6. PMID: 17085682.
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  12. Kriege M, et al. Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy. Br J Cancer. 2014. 111:1004-13. PMID: 24918820.
  13. AlDubayan SH, et al. Association of Inherited Pathogenic Variants in Checkpoint Kinase 2 (CHEK2) With Susceptibility to Testicular Germ Cell Tumors. JAMA Oncol. 2019 5:514-522. PMID: 30676620.
  14. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2020 Sep 14]. Available from
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  16. Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V 1.2021. May 6. Available at
  17. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic. V 1.2022. Aug 11. Available at
Last Updated on 20-Jul-2023