Evidence map›Paper›PMID 30171229›Full record

ArticleProstate cancer and prostatic diseases2019

Prevalence of DNA repair gene mutations in localized prostate cancer according to clinical and pathologic features: association of Gleason score and tumor stage.

Catherine Handy Marshall, Wei Fu, Hao Wang, Alexander S Baras, Tamara L Lotan, Emmanuel S Antonarakis

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PubMed Full text at PMC Publisher
In one paragraph

Article in Prostate cancer and prostatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 5 pooled it
9.3field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 5 syntheses or guidelines pooled it, 93 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Catherine Handy MarshallSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Wei FuSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Hao WangSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Alexander S BarasDepartment of Pathology, Johns Hopkins School University of Medicine, Baltimore, MD, USA.
Tamara L LotanDepartment of Pathology, Johns Hopkins School University of Medicine, Baltimore, MD, USA.
Emmanuel S AntonarakisSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. eantona1@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · USSidney Kimmel Comprehensive Cancer Center · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

backgroundDNA repair gene mutations are present in 8-10% of localized prostate cancers. It is unknown whether this is influenced by clinicopathologic factors.

methodsWe interrogated localized prostate adenocarcinomas with tumor DNA sequencing information from the TCGA validated (n = 333) and Nature Genetics (n = 377) datasets. Homologous recombination repair genes included in our analysis were: ATM, BRCA1/2, CDK12, CHEK1/2, FANCA, FANCD2, FANCL, GEN1, NBN, PALB2, RAD51, and RAD51C. Proportions of cases with pathogenic DNA repair mutations (and in ATM/BRCA1/2 specifically) were reported by Gleason grade group, clinical T, pathologic T, and pathologic N stage. Odds ratios and Fisher's exact tests were used to compare proportions between categories.

resultsPatients with Gleason grade groups 3 and higher were 2.2 times more likely to harbor any DNA repair mutation (95% CI: 1.2-4.2; 10.3% versus 5.0%) and were 2.7 times more likely to have BRCA1/2 or ATM mutations (95% CI: 1.3-6.6; 7.0% versus 2.7%) compared to those in Gleason grade groups 1-2. Patients with pathologic T3 and T4 stage (pT3/pT4) were 2.6 times more likely to have any DNA repair mutation (95% CI: 1.3-6.6; 13.0% versus 5.5%) and were 3.2 times more likely to have BRCA1/2 or ATM mutations (95% CI: 1.2-11.3; 9.5% versus 3.1%) compared to those with pT2 disease. There was no difference by clinical tumor or nodal stage. Among men with Gleason grade group ≥ 3 and clinical stage ≥ cT3, 21.3% (1 in 5) had a DNA repair mutation in any gene and 11.7% (1 in 9) had a mutation in ATM/BRCA1/2.

conclusionsThe prevalence of pathogenic DNA repair gene alterations is enriched in men with advanced tumor stages and higher Gleason grade groups, with maximal enrichment observed in those with Gleason grade group ≥ 3 and clinical stage ≥ cT3 disease. This information can be used to guide eligibility criteria for genomically targeted clinical trials in the neoadjuvant/adjuvant settings.

Indexed as

Biomarkers, TumorDNA RepairGenetic Association StudiesGenetic Predisposition to DiseaseMutationAllelesDatabases, FactualGene FrequencyHumansMaleNeoplasm GradingNeoplasm StagingOdds RatioProstatic NeoplasmsBiomarkers, Tumor

Identifiers

PMID30171229
PMCPMC6372344
OpenAlexW2889358404

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.