Case-Control Study for 23 Cancer Types With Functional Analysis of CHEK2: Risk Estimation and Clinical
Yuri Takehara1,2, Yoshiaki Usui1, Lenka Stolařová3
1Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
JCO Precision Oncology
|September 2, 2025
Summary
Germline damaging variants in the CHEK2 gene increase the risk of female breast and prostate cancer in East Asian populations. Standard cancer screening is recommended for CHEK2 variant carriers in this region.
Area of Science:
- Genetics
- Oncology
- Population Health
Background:
- CHEK2 is a known breast cancer-predisposing gene.
- Evidence for CHEK2's role in other cancers and its clinical relevance in East Asia is limited.
Purpose of the Study:
- To investigate the clinical relevance of CHEK2 germline damaging variants (gDVs) in East Asian populations.
- To assess the association of CHEK2 gDVs with the risk of 23 cancer types.
Main Methods:
- Targeted sequencing and functional analysis of CHEK2 in 111,571 East Asian individuals.
- Definition of germline damaging variants (gDVs) based on ClinVar, prediction, and functional data.
- Association analysis between CHEK2 gDVs and cancer risks, alongside comparison of clinical characteristics.
Main Results:
- Identified 77 CHEK2 gDVs, including 36 functionally impaired missense variants.
- CHEK2 gDVs were significantly associated with female breast cancer (OR=1.8) and prostate cancer (OR=1.8).
- No differences in clinical characteristics or prognosis were observed between carriers and non-carriers; no association with other high-incidence cancers in East Asia.
Conclusions:
- CHEK2 gDVs are linked to increased risks of female breast and prostate cancer in East Asians.
- Careful consideration of systematic clinical management for CHEK2 gDV carriers is needed.
- Standard cancer screening is advised for CHEK2 gDV carriers in East Asia, pending other predisposition indicators.
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