Evidence map›Paper›PMID 27989354›Full record

ArticleEuropean urology2017

Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death.

Rong Na, S Lilly Zheng, Misop Han, Hongjie Yu, Deke Jiang, Sameep Shah, Charles M Ewing, Liti Zhang, Kristian Novakovic, Jacqueline Petkewicz and 27 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05295407 (Observational and Prospective Study on the Performance of Inherited Risk Assessment for Predicting Prostate Cancer From Prostate Biopsy), which is not on this map. Cited by 182 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed, 3 pooled it
21.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT05295407 recruitingnot on this mapstarted 2021, after this paper: background citation

Observational and Prospective Study on the Performance of Inherited Risk Assessment for Predicting Prostate Cancer From Prostate Biopsy (GenBx)

Typeobservational_patient_registrySponsorEndeavor HealthRan2021 to 2027Enrolled1,000ConditionsProstate CancerArmsGenetic Assessment
3 · Its place in the literature

Who cites it

182 citing papers in PubMed, 3 syntheses or guidelines pooled it, 337 citations in OpenAlex.

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122 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors at 6 institutions in 2 countries.

Rong NaFudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China; Program for Isaacs Personalized Cancer Care, IL, USA.
S Lilly ZhengProgram for Isaacs Personalized Cancer Care, IL, USA; Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
Misop HanDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hongjie YuProgram for Isaacs Personalized Cancer Care, IL, USA; State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Deke JiangProgram for Isaacs Personalized Cancer Care, IL, USA; State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Sameep ShahProgram for Isaacs Personalized Cancer Care, IL, USA.
Charles M EwingDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Liti ZhangDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kristian NovakovicProgram for Isaacs Personalized Cancer Care, IL, USA; Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
Jacqueline PetkewiczProgram for Isaacs Personalized Cancer Care, IL, USA; Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
Kamalakar GulukotaDepartment of Center for Molecular Medicine, NorthShore University HealthSystem, Evanston, Illinois, USA.
Donald L HelsethDepartment of Center for Molecular Medicine, NorthShore University HealthSystem, Evanston, Illinois, USA.
Margo QuinnProgram for Isaacs Personalized Cancer Care, IL, USA; Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
Elizabeth HumphriesDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kathleen E WileyDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sarah D IsaacsDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yishuo WuFudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Xu LiuProgram for Isaacs Personalized Cancer Care, IL, USA; State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Ning ZhangFudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China; Program for Isaacs Personalized Cancer Care, IL, USA.
Chi-Hsiung WangProgram for Isaacs Personalized Cancer Care, IL, USA.
Janardan KhandekarDepartment of Center for Molecular Medicine, NorthShore University HealthSystem, Evanston, Illinois, USA.
Peter J HulickDepartment of Medicine, NorthShore University HealthSystem, Evanston, IL, USA.
Daniel H ShevrinDepartment of Medicine, NorthShore University HealthSystem, Evanston, IL, USA.
Kathleen A CooneyDepartment of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
Zhoujun ShenFudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Alan W PartinDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
H Ballentine CarterDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael A CarducciSidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Mario A EisenbergerSidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Sam R DenmeadeSidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Michael McGuireDepartment of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
Patrick C WalshDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Brian T HelfandProgram for Isaacs Personalized Cancer Care, IL, USA; Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
Charles B BrendlerProgram for Isaacs Personalized Cancer Care, IL, USA; Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
Qiang DingFudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: qiangd.urol@gmail.com.
Jianfeng XuFudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China; Program for Isaacs Personalized Cancer Care, IL, USA; Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA; State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China. Electronic address: jxu@northshore.org.
William B IsaacsDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: wisaacs@jhmi.edu.
NorthShore University HealthSystem · USJohns Hopkins University · USFudan University · CNJohns Hopkins Medicine · USHuashan Hospital · CNSidney Kimmel Comprehensive Cancer Center · US

Funding

Targeting FOXA1-downstream pathways: a novel therapeutic strategy for castration-resistant prostate cancerP50CA180995 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ABDULKADIR, SARKI A., HUSSAIN, MAHA H · 2015 to 2025
$19.9M
NCI NIH HHS P50 CA180995
6 · The paper itself

Abstract

backgroundGermline mutations in BRCA1/2 and ATM have been associated with prostate cancer (PCa) risk.

objectiveTo directly assess whether germline mutations in these three genes distinguish lethal from indolent PCa and whether they confer any effect on age at death. DESIGN, SETTING, AND

participantsA retrospective case-case study of 313 patients who died of PCa and 486 patients with low-risk localized PCa of European, African, and Chinese descent. Germline DNA of each of the 799 patients was sequenced for these three genes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Mutation carrier rates and their effect on lethal PCa were analyzed using the Fisher's exact test and Cox regression analysis, respectively. RESULTS AND LIMITATIONS: The combined BRCA1/2 and ATM mutation carrier rate was significantly higher in lethal PCa patients (6.07%) than localized PCa patients (1.44%), p=0.0007. The rate also differed significantly among lethal PCa patients as a function of age at death (10.00%, 9.08%, 8.33%, 4.94%, and 2.97% in patients who died ≤ 60 yr, 61-65 yr, 66-70 yr, 71-75 yr, and over 75 yr, respectively, p=0.046) and time to death after diagnosis (12.26%, 4.76%, and 0.98% in patients who died ≤ 5 yr, 6-10 yr, and>10 yr after a PCa diagnosis, respectively, p=0.0006). Survival analysis in the entire cohort revealed mutation carriers remained an independent predictor of lethal PCa after adjusting for race and age, prostate-specific antigen, and Gleason score at the time of diagnosis (hazard ratio=2.13, 95% confidence interval: 1.24-3.66, p=0.004). A limitation of this study is that other DNA repair genes were not analyzed.

conclusionsMutation status of BRCA1/2 and ATM distinguishes risk for lethal and indolent PCa and is associated with earlier age at death and shorter survival time. PATIENT SUMMARY: Prostate cancer patients with inherited mutations in BRCA1/2 and ATM are more likely to die of prostate cancer and do so at an earlier age.

Indexed as

Germ-Line MutationAgedAge FactorsAsian PeopleAtaxia Telangiectasia Mutated ProteinsBlack PeopleBRCA1 ProteinBRCA2 ProteinCase-Control StudiesHumansMaleMiddle AgedNeoplasm GradingPrognosisProportional Hazards ModelsProstatic NeoplasmsAtaxia Telangiectasia Mutated ProteinsATM protein, humanBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanDNA repair genesGermlineLethal prostate cancerMutation

Identifiers

PMID27989354
PMCPMC5535082
OpenAlexW2567290427

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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.