ArticleInternational journal of cancer2007
Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts.
Article in International journal of cancer, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Pooled it
- Association Between CHEK2*1100delC and Breast Cancer: A Systematic Review and Meta-Analysis.Molecular diagnosis & therapy · 2018Pooled it
- Contribution of large genomic rearrangements in BRCA1/2 genes and CHEK2 1100delC allele variant to the development of breast/ovarian cancer in Argentinian population.Breast cancer research and treatment · 2025Article
- A missense variant effect map for the human tumor-suppressor protein CHK2.American journal of human genetics · 2024Article
- Comprehensive analysis of the functional impact of single nucleotide variants of human CHEK2.PLoS genetics · 2024Article
- The genomic landscape of breast and non-breast cancers from individuals with germline CHEK2 deficiency.JNCI cancer spectrum · 2024Article
- Evaluating the role of CHEK2 p.(Asp438Tyr) allele in inherited breast cancer predisposition.Familial cancer · 2023Article
- Non-BRCA1/BRCA2 high-risk familial breast cancers are not associated with a high prevalence of BRCAness.Breast cancer research : BCR · 2023Article
- Article
- Functional Analysis Identifies Damaging CHEK2 Missense Variants Associated with Increased Cancer Risk.Cancer research · 2022Article
- A Case Report of CHEK2 and MUTYH Germline Mutations Associated With Cholangiocarcinoma in a Young Patient.Cureus · 2022Article
- Common clonal origin of chronic myelomonocytic leukemia and B-cell acute lymphoblastic leukemia in a patient with a germlineCold Spring Harbor molecular case studies · 2021Article
- Population-Based Estimates of the Age-Specific Cumulative Risk of Breast Cancer for Pathogenic Variants inCancers · 2021Article
- Germline mutational spectrum in Armenian breast cancer patients suspected of hereditary breast and ovarian cancer.Human genome variation · 2021Article
- Review
- Variants of uncertain clinical significance in hereditary breast and ovarian cancer genes: best practices in functional analysis for clinical annotation.Journal of medical genetics · 2020Review
- Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population.BMC medical genomics · 2020Article
- Germline variants in cancer genes in high-risk non-BRCA patients from Puerto Rico.Scientific reports · 2019Article
- The impact of variant classification on the clinical management of hereditary cancer syndromes.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 1 country.
Funding
Abstract
The CHEK2-1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer. To identify additional CHEK2 mutations potentially contributing to breast cancer susceptibility, we sequenced 248 cases with early-onset disease; functionally characterized new variants and conducted a population-based case-control analysis to evaluate their contribution to breast cancer risk. We identified 1 additional null mutation and 5 missense variants in the germline of cancer patients. In vitro, the CHEK2-H143Y variant resulted in gross protein destabilization, while others had variable suppression of in vitro kinase activity using BRCA1 as a substrate. The germline CHEK2-1100delC mutation was present among 8/1,646 (0.5%) sporadic, 2/400 (0.5%) early-onset and 3/302 (1%) familial breast cancer cases, but undetectable amongst 2,105 multiethnic controls, including 633 from the US. CHEK2-positive breast cancer families also carried a deleterious BRCA1 mutation. 1100delC appears to be the only recurrent CHEK2 mutation associated with a potentially significant contribution to breast cancer risk in the general population. Another recurrent mutation with attenuated in vitro function, CHEK2-P85L, is not associated with increased breast cancer susceptibility, but exhibits a striking difference in frequency across populations with different ancestral histories. These observations illustrate the importance of genotyping ethnically diverse groups when assessing the impact of low-penetrance susceptibility alleles on population risk. Our findings highlight the notion that clinical testing for rare missense mutations within CHEK2 may have limited value in predicting breast cancer risk, but that testing for the 1100delC variant may be valuable in phenotypically- and geographically-selected populations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.