From the Guidelines
For a 53-year-old male with a CHEK2 gene mutation, recommended screening should include annual prostate-specific antigen (PSA) surveillance, colonoscopy every 5 years beginning at age 40 or 10 years before the earliest colorectal cancer diagnosis in the family, and consideration of enhanced screening for other cancers based on family history. According to the most recent and highest quality study 1, CHEK2 heterozygotes with truncating variants may benefit from annual PSA surveillance, especially in patients with a strong family history of prostate cancer.
Screening Recommendations
- Prostate cancer screening with PSA testing is recommended, especially for those with a strong family history of prostate cancer 1.
- Colonoscopy every 5 years beginning at age 40 or 10 years before the earliest colorectal cancer diagnosis in the family is suggested, as the risk of colorectal cancer is moderate and may be influenced by family history 1.
- There is no evidence for an increased risk for ovarian cancer in CHEK2 heterozygotes, and therefore, risk-reducing salpingo-oophorectomy is not recommended based on CHEK2 status alone 1.
- Breast cancer screening is not specifically recommended for male CHEK2 carriers based on CHEK2 status alone, but rather on family history and other modifiers 1.
Personalized Risk Assessment
A personalized risk assessment is crucial in directing the level of cancer surveillance, taking into account family history, type of CHEK2 variant, and other modifying factors 1. Tools such as CanRisk can generate a personalized risk figure, which can then be used alongside country-specific guidelines to direct surveillance according to the level of risk 1.
Importance of Family History
Family history plays a significant role in determining the risk of cancer in CHEK2 heterozygotes, and therefore, a strong family history of cancer may warrant enhanced screening and surveillance 1. Consultation with a genetic counselor and specialists in cancer genetics is essential to develop a personalized surveillance plan that takes into account the individual's unique risk factors and family history 1.
From the Research
Screening Tests for Prostate Cancer
The following screening tests are recommended for a 53-year-old male with a CHEK2 gene mutation:
- Prostate-specific antigen (PSA) testing 2, 3
- Digital rectal examination (DRE) 2
- Prostate Imaging-Reporting and Data System (PI-RADS) 4
- Transrectal ultrasound-guided biopsy 4
Biomarkers for Prostate Cancer
In addition to PSA, other biomarkers that may be used to supplement screening include:
- Percent free PSA 3
- Prostate health index (PHI) 3
- 4K score 3
- Progensa PCA3 3
- Tissue-based multigene tests such as Decipher, Oncotype DX (Prostate), Prolaris, and ProMark 3
Risk Assessment
Men with a CHEK2 gene mutation are at increased risk of prostate cancer 5, 4, and screening should be considered in men with a familial history of prostate cancer 5. The CHEK2 gene mutation has been associated with an increased risk of prostate cancer, with a pooled odds ratio of 1.98 (1.23-3.18) for unselected cases and 3.39 (1.78-6.47) for familial cases 5.