Evidence map›Paper›PMID 33956343›Full record

ArticleThe Prostate2021

A polymorphism in the promoter of FRAS1 is a candidate SNP associated with metastatic prostate cancer.

Victoria Wang, Milan S Geybels, Kristina M Jordahl, Travis Gerke, Anis Hamid, Kathryn L Penney, Sarah C Markt, Matthew Freedman, Mark Pomerantz, Gwo-Shu M Lee and 15 more

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

Article in The Prostate, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01221168 (ProGene), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 23% 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.

NCT01221168 recruitingnot on this map

ProGene: Etude Genetique et Epidemiologique du Cancer de la Prostate Familial

TypeobservationalSponsorCentre de Recherche sur les Pathologies ProstatiquesRan1996 to 2026Enrolled10,000ConditionsProstate Cancer
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 7 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

25 authors at 13 institutions in 8 countries.

Victoria WangDepartment of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Milan S GeybelsDivision of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington, USA.
Kristina M JordahlDivision of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington, USA.
Travis GerkeCancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
Anis HamidDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
Kathryn L PenneyDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Sarah C MarktDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.ORCID 0000-0003-2873-0358
Matthew FreedmanDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
Mark PomerantzDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
Gwo-Shu M LeeDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.ORCID 0000-0001-9236-9195
Huma RanaDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
Daniela BörnigenUniversity Medical Center Hamburg-Eppendorf, Bioinformatics Core, Hamburg, Germany.
Timothy R RebbeckDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Curtis HuttenhowerDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.
Ros A EelesOncogenetics, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Janet L StanfordDivision of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington, USA.
Practical ConsortiumProstate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Frank ClaessensMolecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Karina D SørensenDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark.
Jong Y ParkDepartment of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
Ana VegaFundación Pública Galega Medicina Xenómica, Santiago de Compostela, Spain.
Nawaid UsmaniDepartment of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
Lorelei MucciDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Christopher J SweeneyDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.ORCID 0000-0002-0398-6018
Dana-Farber Cancer Institute · USHarvard University · USAarhus University Hospital · DKBroad Institute · USFred Hutch Cancer Center · USAlberta Cancer Foundation · CAAltera (United States) · USBrigham and Women's Hospital · USCase Western Reserve University · USMaastricht University · NLMoffitt Cancer Center · USNational Cancer Institute · USRoyal Marsden NHS Foundation Trust · GB

Funding

Project-006U10CA180820 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer · 2014 to 2026
$167.6M
CANCER AND LEUKEMIA GROUP B MINORITY SATELLITE SUPPLEMENU10CA031946 · NCI · UNIVERSITY OF CHICAGO · PI BERTAGNOLLI, MONICA M · 1985 to 2013
$158.4M
SWOG - Foreign Accrual under UMiU10CA032102 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BLANKE, CHARLES D. · 1985 to 2013
$141.3M
ECOG OPERATIONS OFFICE (IBCSG)U10CA021115 · NCI · UNIVERSITY OF WISCONSIN MADISON · PI COMIS, ROBERT L · 1985 to 2013
$132.6M
Statistics CoreU10CA180794 · NCI · DANA-FARBER CANCER INST · PI PAUL J CATALANO, CONSTANTINE A. GATSONIS · 2014 to 2026
$111.2M
ECOG-ACRIN Biospecimen Bank to Support NCTNU24CA196172 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI STANLEY R. HAMILTON, Scott D Jewell · 2015 to 2026
$41.1M
ECOG Statistical Office Data Management GrantU10CA066636 · NCI · FRONTIER SCI &TECHNOLOGY RSCH FDN, INC · PI GRAY, ROBERT J · 1994 to 2013
$39.5M
Tumor and Circulating Markers as Links Between Obesity and Lethal Prostate CanceP50CA090381 · NCI · DANA-FARBER CANCER INSTITUTE · PI KANTOFF, PHILIP W · 2002 to 2017
$36.2M
PROVIDE STATISTICAL SERVICESU10CA023318 · NCI · DANA-FARBER CANCER INSTITUTE · PI GRAY, ROBERT J · 1985 to 2013
$33.4M
Physicians' Health Study II: Prevention Trial of VitaminsR01CA097193 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI GAZIANO, J. MICHAEL · 2002 to 2011
$15.7M
Cancer Epidemiology Cohort in Male Health ProfessionalsUM1CA167552 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2012 to 2016
$11.5M
SOUTHERN NEVADA CANCER RESEARCH FOUNDATION-CCOPU10CA035421 · NCI · SOUTHERN NEVADA CANCER RESEARCH FDN · PI ELLERTON, JOHN A · 1985 to 2014
$9.8M
Department of HealthNCI NIH HHS N01 CA004919NCI NIH HHS N01 CA032102NCI NIH HHS P50 CA090381NCI NIH HHS R01 CA034944NCI NIH HHS R01 CA040360NCI NIH HHS R01 CA056678NCI NIH HHS R01 CA092579NCI NIH HHS R01 CA097193NCI NIH HHS R01 CA131945NCI NIH HHS R01 CA133891NCI NIH HHS R01 CA136578NCI NIH HHS R01 CA141298NCI NIH HHS R03 CA121871NCI NIH HHS R03 CA137799NCI NIH HHS U10 CA004919NCI NIH HHS U10 CA013650NCI NIH HHS U10 CA014548NCI NIH HHS U10 CA016116NCI NIH HHS U10 CA021076NCI NIH HHS U10 CA021115NCI NIH HHS U10 CA023318NCI NIH HHS U10 CA027525NCI NIH HHS U10 CA031946NCI NIH HHS U10 CA032102NCI NIH HHS U10 CA035421NCI NIH HHS U10 CA049883NCI NIH HHS U10 CA066636NCI NIH HHS U10 CA107868NCI NIH HHS U10 CA180794NCI NIH HHS U10 CA180820NCI NIH HHS U24 CA196172NCI NIH HHS UM1 CA167552NHLBI NIH HHS R01 HL026490NHLBI NIH HHS R01 HL034595
6 · The paper itself

Abstract

backgroundInflammation and one of its mediators, NF-kappa B (NFκB), have been implicated in prostate cancer carcinogenesis. We assessed whether germline polymorphisms associated with NFκB are associated with the risk of developing lethal disease (metastases or death from prostate cancer).

methodsUsing a Bayesian approach leveraging NFκB biology with integration of publicly available datasets we used a previously defined genome-wide functional association network specific to NFκB and lethal prostate cancer. A dense-module-searching method identified modules enriched with significant genes from a genome-wide association study (GWAS) study in a discovery data set, Physicians' Health Study and Health Professionals Follow-up Study (PHS/HPFS). The top 48 candidate single nucleotide polymorphisms (SNPs) from the dense-module-searching method were then assessed in an independent prostate cancer cohort and the one SNP reproducibly associated with lethality was tested in a third cohort. Logistic regression models evaluated the association between each SNP and lethal prostate cancer. The candidate SNP was assessed for association with lethal prostate cancer in 6 of 28 studies in the prostate cancer association group to investigate cancer associated alterations in the genome (PRACTICAL) Consortium where there was some medical record review for death ascertainment which also had SNP data from the ONCOARRAY platform. All men self-identified as Caucasian.

resultsThe rs1910301 SNP which was reproducibly associated with lethal disease was nominally associated with lethal disease (odds ratio [OR] = 1.40; p = .02) in the discovery cohort and the minor allele was also associated with lethal disease in two independent cohorts (OR = 1.35; p = .04 and OR = 1.35; p = .07). Fixed effects meta-analysis of all three cohorts found an association: OR = 1.37 (95% confidence interval [CI]: 1.15-1.62, p = .0003). This SNP is in the promoter region of FRAS1, a gene involved in epidermal-basement membrane adhesion and is present at a higher frequency in men with African ancestry. No association was found in the subset of studies from the PRACTICAL consortium studies which had a total of 106 deaths out total of 3263 patients and a median follow-up of 4.4 years.

conclusionsThrough its connection with the NFκB pathway, a candidate SNP with a higher frequency in men of African ancestry without cancer was found to be associated with lethal prostate cancer across three well-annotated independent cohorts of Caucasian men.

Indexed as

AdultAgedAged, 80 and overCohort StudiesExtracellular Matrix ProteinsFollow-Up StudiesGenetic Association StudiesGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotidePromoter Regions, GeneticProstatic NeoplasmsExtracellular Matrix ProteinsFRAS1 protein, humanAfrican ancestrynuclear factor kappa Bsingle nucleotide polymorphismsSNPs

Identifiers

PMID33956343
PMCPMC8491321
OpenAlexW3158043083

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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.