ArticleOncotarget2015
Systematic evaluation of underlying defects in DNA repair as an approach to case-only assessment of familial prostate cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Pooled it
- A systematic review of the prevalence of DNA damage response gene mutations in prostate cancer.International journal of oncology · 2019Pooled it
- Candidate variants in DNA replication and repair genes in early-onset renal cell carcinoma patients referred for germline testing.BMC genomics · 2023Article
- Therapeutic implications of germline vulnerabilities in DNA repair for precision oncology.Cancer treatment reviews · 2022Review
- Biomarkers of therapeutic response with immune checkpoint inhibitors.Annals of translational medicine · 2021Review
- The effect of neighborhood social environment on prostate cancer development in black and white men at high risk for prostate cancer.PloS one · 2020Article
- A Hierarchical Machine Learning Model to Discover Gleason Grade-Specific Biomarkers in Prostate Cancer.Diagnostics (Basel, Switzerland) · 2019Article
- Existing and Emerging Biomarkers for Immune Checkpoint Immunotherapy in Solid Tumors.Advances in therapy · 2019Review
- Molecular mechanisms of the preventable causes of cancer in the United States.Genes & development · 2018Review
- Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods.Cancer biology & therapy · 2017Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Risk assessment for prostate cancer is challenging due to its genetic heterogeneity. In this study, our goal was to develop an operational framework to select and evaluate gene variants that may contribute to familial prostate cancer risk. Drawing on orthogonal sources, we developed a candidate list of genes relevant to prostate cancer, then analyzed germline exomes from 12 case-only prostate cancer patients from high-risk families to identify patterns of protein-damaging gene variants. We described an average of 5 potentially disruptive variants in each individual and annotated them in the context of public databases representing human variation. Novel damaging variants were found in several genes of relevance to prostate cancer. Almost all patients had variants associated with defects in DNA damage response. Many also had variants linked to androgen signaling. Treatment of primary T-lymphocytes from these prostate cancer patients versus controls with DNA damaging agents showed elevated levels of the DNA double strand break (DSB) marker γH2AX (p < 0.05), supporting the idea of an underlying defect in DNA repair. This work suggests the value of focusing on underlying defects in DNA damage in familial prostate cancer risk assessment and demonstrates an operational framework for exome sequencing in case-only prostate cancer genetic evaluation.
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Registered trials
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.