ArticleJournal of the National Cancer Institute2021
Germline Sequencing DNA Repair Genes in 5545 Men With Aggressive and Nonaggressive Prostate Cancer.
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 39 papers.
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Who cites it
39 citing papers in PubMed, 87 citations in OpenAlex.
- RETRACTED: Polygenic risk score and prostate specific antigen predict death from prostate cancer in men with intermediate aggressive cancer.International journal of cancer · 2026Article
- Integrating Pathogenic Variants, Polygenic Risk Score, and Family History for Prostate Cancer Risk Estimation in Men of African Ancestry.European urology · 2026Article
- Developing a germline prostate cancer risk test incorporating rare and common variants, to inform clinical decisions: a route to precision oncology.Genome medicine · 2026Article
- Exploring the genetic overlap between obstructive sleep apnea and prostate cancer.Journal of the National Cancer Center · 2026Article
- Identifying Patients at Risk of Early Lethal Prostate Cancer by Integrating Family History, Polygenic Risk Score, Rare Variants in DNA Repair Genes, and Lifestyle Factors.European urology oncology · 2026Article
- Genomic landscape and precision therapy in prostate cancer: current status and future directions.NPJ precision oncology · 2026Review
- Identifying and characterizing the germinal genetic landscape of men with prostate cancer: A real-life, retrospective, multicenter study.Genetics in medicine open · 2026Article
- Article
- Germline Testing for Prostate Cancer Patients: Evidence-Based Evaluation of Genes Recommended by NCCN Guidelines.The Prostate · 2025Article
- Review
- Germline DNA Damage Repair Variants and Prognosis of Patients with High-Risk or Metastatic Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Exploring the Common Mutational Landscape in Cutaneous Melanoma and Pancreatic Cancer.Pigment cell & melanoma research · 2025Review
- Predictive Genetic Testing in the Cancer Management and Prevention.Journal of cancer science and clinical therapeutics · 2025Article
- Clinical relevance of protein-truncating variants of germline DNA repair genes in prostate cancer.BMC cancer · 2024Article
- Article
- Prostate cancer genotyping for risk stratification and precision treatment.Current urology · 2024Review
- Identification of Genes with Rare Loss of Function Variants Associated with Aggressive Prostate Cancer and Survival.European urology oncology · 2024Article
- Article
- Impact of germline DNA repair gene variants on prognosis and treatment of men with advanced prostate cancer.Scientific reports · 2023Article
- Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer.JAMA oncology · 2023Article
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Authors and funding
30 authors at 13 institutions in 7 countries.
Funding
Abstract
backgroundThere is an urgent need to identify factors specifically associated with aggressive prostate cancer (PCa) risk. We investigated whether rare pathogenic, likely pathogenic, or deleterious (P/LP/D) germline variants in DNA repair genes are associated with aggressive PCa risk in a case-case study of aggressive vs nonaggressive disease.
methodsParticipants were 5545 European-ancestry men, including 2775 nonaggressive and 2770 aggressive PCa cases, which included 467 metastatic cases (16.9%). Samples were assembled from 12 international studies and germline sequenced together. Rare (minor allele frequency < 0.01) P/LP/D variants were analyzed for 155 DNA repair genes. We compared single variant, gene-based, and DNA repair pathway-based burdens by disease aggressiveness. All statistical tests are 2-sided.
resultsBRCA2 and PALB2 had the most statistically significant gene-based associations, with 2.5% of aggressive and 0.8% of nonaggressive cases carrying P/LP/D BRCA2 alleles (odds ratio [OR] = 3.19, 95% confidence interval [CI] = 1.94 to 5.25, P = 8.58 × 10-7) and 0.65% of aggressive and 0.11% of nonaggressive cases carrying P/LP/D PALB2 alleles (OR = 6.31, 95% CI = 1.83 to 21.68, P = 4.79 × 10-4). ATM had a nominal association, with 1.6% of aggressive and 0.8% of nonaggressive cases carrying P/LP/D ATM alleles (OR = 1.88, 95% CI = 1.10 to 3.22, P = .02). In aggregate, P/LP/D alleles within 24 literature-curated candidate PCa DNA repair genes were more common in aggressive than nonaggressive cases (carrier frequencies = 14.2% vs 10.6%, respectively; P = 5.56 × 10-5). However, this difference was non-statistically significant (P = .18) on excluding BRCA2, PALB2, and ATM. Among these 24 genes, P/LP/D carriers had a 1.06-year younger diagnosis age (95% CI = -1.65 to 0.48, P = 3.71 × 10-4).
conclusionsRisk conveyed by DNA repair genes is largely driven by rare P/LP/D alleles within BRCA2, PALB2, and ATM. These findings support the importance of these genes in both screening and disease management considerations.
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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.