Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review

CHEK2-Related Cancer Predisposition

Helen Hanson  1 , Tuya Pal  2 , Marc Tischkowitz  3 , Douglas Stewart  4
Margaret P Adam, Sarah Bick, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Anne Amemiya
, editors.
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
.
Affiliations
Free Books & Documents
Review

CHEK2-Related Cancer Predisposition

Helen Hanson et al.
Free Books & Documents

Excerpt

Clinical characteristics: CHEK2-related cancer predisposition is predominantly characterized by an increased risk of female breast cancer. To a lesser extent there is an association with increased risk of prostate cancer. Associations for other cancers are less well established or conflicting. Cancer risks in those with CHEK2-related cancer predisposition can vary considerably depending on modifying factors such as family history.

Diagnosis/testing: The diagnosis of CHEK2-related cancer predisposition is established in a proband with a heterozygous germline pathogenic variant in CHEK2 identified by molecular genetic testing.

Management: Treatment of manifestations: Standard cancer treatments are recommended. Breast cancer risk-reducing contralateral mastectomy is generally not recommended but may be considered in some situations.

Surveillance: Breast cancer surveillance in females typically includes breast self-exam training and symptom awareness; mammogram every 12 months beginning at age 40 years; breast MRI recommendations vary by location. Prostate cancer surveillance in males includes serum PSA to be considered annually beginning at age 40 years especially in those with a strong family history of prostate cancer.

Evaluation of relatives at risk: Molecular genetic testing of at-risk female and male adult relatives can identify those family members who also have the familial pathogenic variant and thus may benefit from increased cancer surveillance.

Genetic counseling: CHEK2-related cancer predisposition is an autosomal dominant disorder (i.e., individuals who have one copy of a CHEK2 pathogenic variant have the disorder). Most individuals with CHEK2-related cancer predisposition have a heterozygous pathogenic variant. Rarely, affected individuals have biallelic pathogenic variants. The vast majority of individuals with a heterozygous germline CHEK2 pathogenic variant inherited the pathogenic variant from a parent who may or may not have had a cancer diagnosis. The offspring of an individual identified as having a heterozygous germline CHEK2 pathogenic variant have a 50% chance of inheriting the pathogenic variant. All offspring of an individual identified as having biallelic germline CHEK2 pathogenic variants will inherit a pathogenic variant. Once the CHEK2 pathogenic variant(s) have been identified in an affected family member, predictive testing for at-risk relatives is possible.

PubMed Disclaimer

References

    1. Agaoglu NB, Bychkovsky BL, Horton C, Lo MT, Polfus L, Carraway C, Hemyari P, Young C, Richardson ME, Scheib R, Garber JE, Rana HQ. Cancer burden in individuals with single versus double pathogenic variants in cancer susceptibility genes. Genet Med Open. 2024;2:101829. - PMC - PubMed
    1. Agiannitopoulos K, Pepe G, Tsaousis GN, Potska K, Bouzarelou D, Katseli A, Ntogka C, Meintani A, Tsoulos N, Giassas S, Venizelos V, Markopoulos C, Iosifidou R, Karageorgopoulou S, Christodoulou C, Natsiopoulos I, Papazisis K, Vasilaki-Antonatou M, Kabletsas E, Psyrri A, Ziogas D, Lalla E, Koumarianou A, Anastasakou K, Papadimitriou C, Ozmen V, Tansan S, Kaban K, Ozatli T, Eniu DT, Chiorean A, Blidaru A, Rinsma M, Papadopoulou E, Nasioulas G. Copy number variations (CNVs) account for 10.8% of pathogenic variants in patients referred for hereditary cancer testing. Cancer Genomics Proteomics. 2023;20:448-55. - PMC - PubMed
    1. Antoniou AC, Casadei S, Heikkinen T, Barrowdale D, Pylkäs K, Roberts J, Lee A, Subramanian D, De Leeneer K, Fostira F, Tomiak E, Neuhausen SL, Teo ZL, Khan S, Aittomäki K, Moilanen JS, Turnbull C, Seal S, Mannermaa A, Kallioniemi A, Lindeman GJ, Buys SS, Andrulis IL, Radice P, Tondini C, Manoukian S, Toland AE, Miron P, Weitzel JN, Domchek SM, Poppe B, Claes KB, Yannoukakos D, Concannon P, Bernstein JL, James PA, Easton DF, Goldgar DE, Hopper JL, Rahman N, Peterlongo P, Nevanlinna H, King MC, Couch FJ, Southey MC, Winqvist R, Foulkes WD, Tischkowitz M. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371:497-506. - PMC - PubMed
    1. Apostolou P, Fostira F, Mollaki V, Delimitsou A, Vlassi M, Pentheroudakis G, Faliakou E, Kollia P, Fountzilas G, Yannoukakos D, Konstantopoulou I. Characterization and prevalence of two novel CHEK2 large deletions in Greek breast cancer patients. J Hum Genet. 2018;63:877-86. - PubMed
    1. Bottillo I, Savino E, Majore S, Mulargia C, Valiante M, Ferraris A, Rossi V, Svegliati F, Ciccone MP, Brusco F, Grammatico B, Di Giacomo G, Bargiacchi S, D'Angelantonio D, Grammatico P. Two unrelated cases with biallelic CHEK2 variants:a novel condition with constitutional chromosomal instability? Eur J Hum Genet. 2023;31:474-8. - PMC - PubMed

LinkOut - more resources