ArticleJournal of the National Cancer Institute2021
Performance of Breast Cancer Polygenic Risk Scores in 760 Female CHEK2 Germline Mutation Carriers.
Article in Journal of the National Cancer Institute, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- A systematic review of prediction models for risk of breast cancer.BMC cancer · 2025Pooled it
- Polygenic risk scores in cancer.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- A New Inverse Probability of Selection Weighted Cox Model to Deal With Outcome-Dependent Sampling in Survival Analysis.Biometrical journal. Biometrische Zeitschrift · 2025Article
- CHEK2-related breast cancer: real-world challenges.Familial cancer · 2025Article
- Translational breast cancer research : a journal focusing on translational research in breast cancer · 2025Review
- Genetic evaluation of patients with multiple primary cancers.Oncology letters · 2025Article
- Limitations in next-generation sequencing-based genotyping of breast cancer polygenic risk score loci.European journal of human genetics : EJHG · 2024Article
- A comprehensive analysis of germline predisposition to early-onset ovarian cancer.Scientific reports · 2024Article
- Article
- Genomes in clinical care.NPJ genomic medicine · 2024Review
- Review
- TheInternational journal of molecular sciences · 2023Article
- An apparent quandary: adoption of polygenics and gene panels for personalised breast cancer risk stratification.BJC reports · 2023Review
- Polygenic risk scores indicate extreme ages at onset of breast cancer in female BRCA1/2 pathogenic variant carriers.BMC cancer · 2022Article
- Are polygenic risk scores ready for the cancer clinic?-a perspective.Translational lung cancer research · 2022Review
- Risk-Adjusted Cancer Screening and Prevention (RiskAP): Complementing Screening for Early Disease Detection by a Learning Screening Based on Risk Factors.Breast care (Basel, Switzerland) · 2022Review
- Polygenic risk scores: the future of cancer risk prediction, screening, and precision prevention.Medical review (2021) · 2021Review
- Management of Women With Breast Cancer and Pathogenic Variants in Genes Other ThanJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Article
Corrections and comments
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Authors and funding
31 authors at 20 institutions in 3 countries.
Funding
Abstract
backgroundGenome-wide association studies suggest that the combined effects of breast cancer (BC)-associated single nucleotide polymorphisms (SNPs) can improve BC risk stratification using polygenic risk scores (PRSs). The performance of PRSs in genome-wide association studies-independent clinical cohorts is poorly studied in individuals carrying mutations in moderately penetrant BC predisposition genes such as CHEK2.
methodsA total of 760 female CHEK2 mutation carriers were included; 561 women were affected with BC, of whom 74 developed metachronous contralateral BC (mCBC). For PRS calculations, 2 SNP sets covering 77 (SNP set 1, developed for BC risk stratification in women unselected for their BRCA1/2 germline mutation status) and 88 (SNP set 2, developed for BC risk stratification in female BRCA1/2 mutation carriers) BC-associated SNPs were used. All statistical tests were 2-sided.
resultsBoth SNP sets provided concordant PRS results at the individual level (r = 0.91, P < 2.20 × 10-16). Weighted cohort Cox regression analyses revealed statistically significant associations of PRSs with the risk for first BC. For SNP set 1, a hazard ratio of 1.71 per SD of the PRS was observed (95% confidence interval = 1.36 to 2.15, P = 3.87 × 10-6). PRSs identify a subgroup of CHEK2 mutation carriers with a predicted lifetime risk for first BC that exceeds the surveillance thresholds defined by international guidelines. Association of PRS with mCBC was examined via Cox regression analysis (SNP set 1 hazard ratio = 1.23, 95% confidence interval = 0.86 to 1.78, P = .26).
conclusionsPRSs may be used to personalize risk-adapted preventive measures for women with CHEK2 mutations. Larger studies are required to assess the role of PRSs in mCBC predisposition.
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