What cancer screening is recommended for individuals with a positive CHEK2 (Checkpoint Kinase 2) genetic test result?

Cancer Screening Recommendations for CHEK2 Genetic Testing Positive Individuals

Cancer screening for individuals with a positive CHEK2 genetic test should be personalized based on family history and variant type, with breast cancer screening being the primary focus, followed by consideration of colorectal and prostate cancer surveillance. 1

Breast Cancer Screening

For individuals with CHEK2 pathogenic/likely pathogenic variants, breast cancer screening recommendations vary based on the type of variant:

For Truncating Variants:

• Enhanced breast cancer surveillance should be guided by:
  • Personalized risk assessment using models like CanRisk
  • Country-specific guidelines for high-risk individuals
  • Family history of breast cancer
  • The lifetime risk of breast cancer is approximately 25% for women with a CHEK2 mutation and family history 2

For Missense Variants:

• Generally lower risk compared to truncating variants
• Breast cancer screening should be based primarily on family history and other risk factors
• Some specific missense variants (e.g., p.Arg117Gly) may warrant enhanced screening

Special Considerations for Breast Cancer:

• Women with CHEK2 mutations who have already had breast cancer have an increased risk of contralateral breast cancer (CBC)
  • Premenopausal women: 10-year cumulative incidence of CBC approximately 13%
  • Postmenopausal women: 10-year cumulative incidence of CBC approximately 4% 1
• MRI screening may be appropriate for women with CHEK2 mutations and family history 2

Colorectal Cancer Screening

• For truncating variants with family history of colorectal cancer: Consider earlier and more frequent colonoscopy screening
  • Starting at age 40 or 10 years before the earliest colorectal cancer diagnosis in a first-degree relative
  • Repeat every 5 years 1
• For truncating variants without family history: Standard population-based screening is generally sufficient
• For missense variants: Base screening on family history and other risk factors, not solely on CHEK2 status
• Recent evidence suggests individuals with CHEK2 c.1100delC may benefit from colorectal surveillance starting at age 45 3

Prostate Cancer Screening

• For men with truncating variants: Consider annual PSA testing, especially with:
  • Strong family history (2 or more affected relatives)
  • History of young-onset or metastatic prostate cancer 1
• For missense variants: Base screening on family history and other risk factors

Other Cancer Considerations

• Ovarian cancer: No increased risk established; risk-reducing salpingo-oophorectomy not recommended based solely on CHEK2 status 1
• Hematological cancers: Some evidence suggests increased risk, particularly with c.1100delC variant 3, but insufficient evidence for specific screening recommendations

Important Caveats

• The penetrance of CHEK2 mutations is lower than BRCA1/2 mutations
• Variant type matters significantly - truncating variants generally confer higher cancer risks than missense variants
• Family history can substantially modify the cancer risk associated with CHEK2 mutations
• Bilateral breast cancer is approximately six times more common in CHEK2 mutation carriers compared to those with unilateral cancer 4
• CHEK2 testing should be considered alongside BRCA1/2 testing in appropriate clinical settings 2

Algorithm for Screening Decisions

1. Determine CHEK2 variant type (truncating vs. missense)
2. Assess family history of cancer (breast, colorectal, prostate)
3. Calculate personalized risk using models like CanRisk when available
4. Apply country-specific guidelines for high-risk screening
5. Consider age-specific recommendations for each cancer type
6. Educate about modifiable risk factors for cancer prevention