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CHEK2 gene

Associated Syndrome Name: CHEK2-associated cancer risk

CHEK2 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
BreastHigh Risk
ColorectalElevated Risk
Male BreastElevated Risk

CHEK2 gene Overview

CHEK2-associated cancer risk 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13
  • Most women with 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. Men with CHEK2 mutations also have an increased risk for breast cancer.
  • Estimates of cancer risk for men and women with CHEK2 mutations vary widely and are strongly influenced by family history. In cases where there is no family history of one of these cancers, the risk for a patient with a CHEK2 mutation may be lower than in cases where that cancer has been diagnosed in one or more close relatives. Therefore, the family history of a patient should be considered when deciding on the most appropriate strategies to manage cancer risk, with more aggressive strategies targeted to patients with significant family histories of related cancers.
  • 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.
  • Some studies have described a possible increased risk for a wide range of cancers in patients with CHEK2 mutations, including prostate, gastric, thyroid, renal, 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. Since information about the cancer risks associated with 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 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
Female BreastTo age 805, 6, 7, 10, 11, 1420%-31%10.7%
Second primary within 10 years of first breast cancer diagnosis4, 15, 16, 177%-29%3.5%
Male BreastTo age 8012, 14, 180.4%-1%0.1%
ColorectalTo age 802, 14Possibly elevated risk2.8%

CHEK2 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 BreastBreast 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.20IndividualizedNA
Clinical encounter, including clinical breast exam, ongoing risk assessment and risk-reduction counseling20When genetic risk is identified, but not before age 21Every 6 to 12 months
Mammography21Age 40, or modified to a younger age based on the family history of breast cancerAnnually
Consider breast MRI with contrast2130 to 35 years, or modified to a younger age based on the family history of breast cancerAnnually
Consider additional risk-reduction strategies.20, 21IndividualizedNA
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.20, 21IndividualizedNA
ColorectalColonoscopy240 years, or 10 years younger than the age of diagnosis for any first-degree relative with colorectal cancerEvery 5 years
For Patients With A Cancer DiagnosisFor patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., PARP-inhibitors).19NANA

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 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.

In rare instances, an individual may inherit mutations in both copies of the CHEK2 gene, leading to significantly higher breast cancer risks than those in women with a single CHEK2 mutation. 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. Alternatively, this patient's children may consider genetic testing for any mutations in the entire CHEK2 gene.22

References

  1. 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.

  2. Gupta S, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 1.2023. May 30. Available at https://www.nccn.org.

  3. Xiang HP, et al. Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility. Eur J Cancer. 2011 47:2546-51. PMID: 21807500.

  4. 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.

  5. 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.

  6. Kurian AW, et al. Breast and Ovarian Cancer Penetrance Estimates Derived From Germline Multiple-Gene Sequencing Results in Women. JCO Precis Oncol. 2017 Nov;1:1-12. PMID: 35172496.

  7. Meijers-Heijboer H, et al. CHEK2-Breast Cancer Consortium. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002 31:55-9. PMID: 11967536.

  8. Teodorczyk U, et al. The risk of gastric cancer in carriers of CHEK2 mutations. Fam Cancer. 2013 12:473-8. PMID: 23296741.

  9. Yngvadottir B, et al. Frequency of pathogenic germline variants in cancer susceptibility genes in 1336 renal cell carcinoma cases. Hum Mol Genet. 2022 31(17):3001-3011. PMID: 35441217.

  10. Weischer et al. CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J Clin Oncol. 2008 26: 542-8. PMID: 18172190.

  11. 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.

  12. Wasielewski M, et al. CHEK2 1100delC and male breast cancer in the Netherlands. Breast Cancer Res Treat. 2009 116:397-400. PMID: 18759107.

  13. 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.

  14. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2023 Mar 24]. Available from https://seer.cancer.gov/explorer/.

  15. Morra A, et al. The impact of coding germline variants on contralateral breast cancer risk and survival. Am J Hum Genet. 2023 Mar 2;110(3):475-486. PMID: 36827971.

  16. Yadav S, et al. Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. J Clin Oncol. 2023 Mar 20;41(9):1703-1713. PMID: 36623243.

  17. Giannakeas V, et al. The risk of contralateral breast cancer: a SEER-based analysis. Br J Cancer. 2021 Aug;125(4):601-610. PMID: 34040177.

  18. Rolfes M, et al. Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer. Cancers (Basel). 2022 14(13):3292. PMID: 35805063.

  19. Schaeffer E, et al. NCCN Clinical Practice Guidelines in Oncology®: Prostate Cancer. V 1.2023. Sep 16. Available at https://www.nccn.org.

  20. Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V 1.2022. Jun 2. Available at https://www.nccn.org.

  21. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic. V 3.2023. Feb 13. Available at https://www.nccn.org.

  22. Rainville I, et al. High risk of breast cancer in women with biallelic pathogenic variants in CHEK2. Breast Cancer Res Treat. 2020 180:503-509. PMID: 31993860.

Last Updated on 31-Jan-2024

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