Evidence map›Paper›PMID 36610996›Full record

ArticleJournal of the National Cancer Institute2023

A polygenic two-hit hypothesis for prostate cancer.

Kathleen E Houlahan, Julie Livingstone, Natalie S Fox, Natalie Kurganovs, Helen Zhu, Jocelyn Sietsma Penington, Chol-Hee Jung, Takafumi N Yamaguchi, Lawrence E Heisler, Richard Jovelin and 11 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Germline polygenic score for prostate cancer aggressiveness.medRxiv : the preprint server for health sciences · 2026
    Article
  2. Article
  3. Article
  4. The landscape of NNature genetics · 2025
    Article
  5. Article
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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

21 authors at 10 institutions in 7 countries.

Kathleen E HoulahanDepartment of Human Genetics, University of California, Los Angeles, CA, USA.ORCID 0000-0002-2273-2099
Julie LivingstoneDepartment of Human Genetics, University of California, Los Angeles, CA, USA.
Natalie S FoxDepartment of Human Genetics, University of California, Los Angeles, CA, USA.
Natalie KurganovsAustralian Prostate Cancer Research Centre Epworth, Richmond, VIC, Australia.
Helen ZhuDepartment of Medical Biophysics, University of Toronto, Toronto, Canada.
Jocelyn Sietsma PeningtonBioinformatics Division, Walter and Eliza Hall Institute, Parkville, VIC, Australia.
Chol-Hee JungMelbourne Bioinformatics, The University of Melbourne, Parkville, VIC, Australia.
Takafumi N YamaguchiDepartment of Human Genetics, University of California, Los Angeles, CA, USA.
Lawrence E HeislerOntario Institute for Cancer Research, Toronto, Canada.
Richard JovelinOntario Institute for Cancer Research, Toronto, Canada.
Anthony J CostelloDivision of Urology, Royal Melbourne Hospital, Parkville, VIC, Australia.
Bernard J PopeDepartment of Surgery, The University of Melbourne, Parkville, VIC, Australia.
Amar U KishanJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA.
Niall M CorcoranAustralian Prostate Cancer Research Centre Epworth, Richmond, VIC, Australia.
Robert G BristowDepartment of Medical Biophysics, University of Toronto, Toronto, Canada.
Sebastian M WaszakCentre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, and Oslo University Hospital, Oslo, Norway.
Joachim WeischenfeldtBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Housheng H HeDepartment of Medical Biophysics, University of Toronto, Toronto, Canada.
Rayjean J HungProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
Christopher M HovensAustralian Prostate Cancer Research Centre Epworth, Richmond, VIC, Australia.
Paul C BoutrosDepartment of Human Genetics, University of California, Los Angeles, CA, USA.
Ontario Institute for Cancer Research · CAProstate Cancer Foundation of Australia · AUUniversity Health Network · CAUniversity of California, Los Angeles · USThe University of Melbourne · AUOslo University Hospital · NOThe Royal Melbourne Hospital · AUUniversity of Copenhagen · DKUniversity of Toronto · CAWalter and Eliza Hall Institute of Medical Research · AU

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Advancing method benchmarking and data sharing through crowd-sourced competitions in cancer researchU24CA248265 · NCI · SAGE BIONETWORKS · PI BOUTROS, PAUL CHRISTOPHER, VARMA, SUSHEEL · 2020 to 2024
$4.1M
NCI NIH HHS P30 CA016042NCI NIH HHS P30CA016042NCI NIH HHS U24 CA248265
6 · The paper itself

Abstract

Prostate cancer is one of the most heritable cancers. Hundreds of germline polymorphisms have been linked to prostate cancer diagnosis and prognosis. Polygenic risk scores can predict genetic risk of a prostate cancer diagnosis. Although these scores inform the probability of developing a tumor, it remains unknown how germline risk influences the tumor molecular evolution. We cultivated a cohort of 1250 localized European-descent patients with germline and somatic DNA profiling. Men of European descent with higher genetic risk were diagnosed earlier and had less genomic instability and fewer driver genes mutated. Higher genetic risk was associated with better outcome. These data imply a polygenic "two-hit" model where germline risk reduces the number of somatic alterations required for tumorigenesis. These findings support further clinical studies of polygenic risk scores as inexpensive and minimally invasive adjuncts to standard risk stratification. Further studies are required to interrogate generalizability to more ancestrally and clinically diverse populations.

Indexed as

Prostatic NeoplasmsGenetic Predisposition to DiseaseHumansMalePrognosisRisk Factors

Identifiers

PMID36610996
PMCPMC10086625
OpenAlexW4313702110

What OpenQuestion holds

Textmetadata
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.