- Hereditary Breast and Ovarian Cancer syndrome (HBOC)
- Lynch syndrome/Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
- Familial Adenomatous Polyposis (FAP)/Attenuated Familial Adenomatous Polyposis (AFAP)
- MUTYH-associated Polyposis syndrome (MAP)
- MUTYH-associated Colon Cancer Risk
- Melanoma Cancer Syndrome (MCS)
- Li-Fraumeni Syndrome (LFS)
- PTEN Hamartoma Tumor syndrome (PHTS)
- Peutz-Jeghers Syndrome
- Hereditary Diffuse Gastric Cancer (HDGC) Syndrome
- Juvenile Polyposis Syndrome (JPS)
- Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT)
- PALB2-associated Cancer Risk
- CHEK2-associated Cancer Risk
- ATM-associated Cancer Risk
- NBN-associated Cancer Risk
- BARD1-associated Cancer Risk
- BRIP1-associated Cancer Risk
- RAD51C-associated Cancer Risk
- RAD51D-associated Cancer Risk
- Polymerase Proofreading-associated Syndrome (PPAS)
- Hereditary Mixed Polyposis Syndrome (HMPS)
CHEK2 ASSOCIATED CANCER RISKS
CHEK2 ASSOCIATED CANCER RISKS
What does it mean to have a CHEK2 gene mutation?
Women with mutations in the CHEK2 gene have an increased risk for breast cancer, sometimes at relatively young ages. This increase in risk is not as high as what is seen in women with mutations in the BRCA1 and BRCA2 genes, but it is high enough to consider ways to reduce cancer risk and to increase screening in an attempt to find any breast cancers that do develop as early as possible. A woman who has a CHEK2 mutation, and who has already had breast cancer, has a high risk of developing a second breast cancer within the next 5 to 25 years.
Men with mutations in the CHEK2 gene also have an increased risk for breast cancer. This risk is much smaller than the risk for women.
What can be done to protect people with CHEK2 mutations from cancer?
Women with CHEK2 mutations may benefit from a variety of options to reduce their risk for breast cancer. This could include starting breast screenings at younger ages than normal and having the screenings more often than typically recommended. The same may be true for prostate cancer and colorectal cancer screenings, especially if there is history of these cancers in the family.
We have only recently discovered that CHEK2 mutations increase cancer risks and as we learn more, there may be new information about risks for other cancers and the best ways to reduce those risks. For this reason, people with CHEK2 mutations may benefit from speaking with healthcare providers who specialize in the genetics of inherited cancer risks.
Associated Syndrome Name: CHEK2-associated Cancer Risk
CHEK2 Summary Cancer Risk Table
|Cancer||Genetic Cancer Risk|
|Female Breast||High Risk|
|Male Breast||Elevated Risk|
CHEK2 gene Overview
CHEK2-associated Cancer Risk 1, 2, 3, 4, 5, 6, 7, 8, 9, 10
- 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.
- Although many different CHEK2 mutations have been identified, estimated cancer risks for CHEK2 are currently based largely on studies of a single mutation (c.1100del) that is common in patients of European ancestry. These estimates may be modified as we learn more about other CHEK2 mutations in patients of varied ancestries.
- Some studies have described a possible increased risk for a wide range of cancers in patients with CHEK2 mutations, including prostate, leukemia, lymphoma, gastric cancer, thyroid cancer 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 Breast||To age 801, 2, 3, 4, 11||23%-48%||10.2%|
|Second primary within 10 years of first breast cancer diagnosis10, 12||Up to 29%||4.0%|
|Male Breast||To age 805, 11||0.4%-1%||0.1%|
|Colorectal||To age 808, 11||Possibly elevated risk||3.0%|
CHEK2 Cancer Risk Management Table
The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details 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 Breast||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.13||Individualized||NA|
|Clinical encounter, including clinical breast exam, ongoing risk assessment and risk-reduction counseling13||When genetic risk is identified||Every 6 to 12 months|
|Mammography with consideration of tomosynthesis and consideration of breast MRI with contrast14||Age 40, or modified to a younger age based on the family history of breast cancer||Annually|
|Consider additional risk-reduction strategies.13, 14||Individualized||NA|
|Male Breast||Currently there are no specific medical management guidelines for 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.13, 14||Individualized||NA|
|Colorectal||Colonoscopy8||40 years, or 10 years younger than the age of diagnosis for any first-degree relative with colorectal cancer||Every 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 gene.
A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.
- 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.
- 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.
- 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.
- 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.
- Wasielewski M, et al. CHEK2 1100delC and male breast cancer in the Netherlands. Breast Cancer Res Treat. 2009 116:397-400. PMID: 18759107.
- 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.
- Xiang HP, et al. Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility. Eur J Cancer. 2011 47:2546-51. PMID: 21807500.
- Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 1.2018. July 12. Available at http://www.nccn.org.
- Teodorczyk U, et al. The risk of gastric cancer in carriers of CHEK2 mutations. Fam Cancer. 2013 12:473-8. PMID: 23296741.
- 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.
- Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
- Curtis RE, et al. New Malignancies Following Breast Cancer. 2006 In: Curtis RE, et al., editors. New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973-2000. National Cancer Institute. NIH Publ. No. 05-5302.
- Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V 2.2018. May 18. Available at http://www.nccn.org.
- Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V 2.2019. July 30. Available at http://www.nccn.org.
Last Updated on 09-Jul-2019