Evidence map›Paper›PMID 42001130›Full record

ArticleGenome medicine2026

Developing a germline prostate cancer risk test incorporating rare and common variants, to inform clinical decisions: a route to precision oncology.

Sarah Wakerell, Questa Karlsson, Susan Merson, Reshma Rageevakumar, Edward Saunders, Dan Burns, Mark N Brook, Tokhir Dadaev, Elizabeth C Page, Sarah Thomas and 9 more

Abstract read
In one paragraph

Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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.

2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

19 authors.

Sarah Wakerell *The Institute of Cancer Research, London, SW7 3RD, UK.
Questa Karlsson *The Institute of Cancer Research, London, SW7 3RD, UK.
Susan Merson *The Institute of Cancer Research, London, SW7 3RD, UK.
Reshma RageevakumarThe Institute of Cancer Research, London, SW7 3RD, UK.
Edward SaundersThe Institute of Cancer Research, London, SW7 3RD, UK.
Dan BurnsThe Institute of Cancer Research, London, SW7 3RD, UK.
Mark N BrookThe Institute of Cancer Research, London, SW7 3RD, UK.
Tokhir DadaevThe Institute of Cancer Research, London, SW7 3RD, UK.
Elizabeth C PageThe Institute of Cancer Research, London, SW7 3RD, UK.
Sarah ThomasThe Royal Marsden NHS Foundation Trust, London, UK.
Natalie TaylorThe Royal Marsden NHS Foundation Trust, London, UK.
Jennifer PopeThe Institute of Cancer Research, London, SW7 3RD, UK.
Shameela CousinsThe Royal Marsden NHS Foundation Trust, London, UK.
Jana McHughThe Institute of Cancer Research, London, SW7 3RD, UK.
Ann-Britt JonesThe Institute of Cancer Research, London, SW7 3RD, UK.
Terri P McVeighThe Institute of Cancer Research, London, SW7 3RD, UK.
Elizabeth K Bancroft *The Institute of Cancer Research, London, SW7 3RD, UK.
Rosalind A Eeles *The Institute of Cancer Research, London, SW7 3RD, UK.
Zsofia Kote-Jarai *The Institute of Cancer Research, London, SW7 3RD, UK. zsofia.kote-jarai@icr.ac.uk.

Funding

Wellcome Trust 201620
6 · The paper itself

Abstract

backgroundPathogenic germline variants in DNA damage response and repair (DDR) genes are established risk factors for prostate cancer (PrCa). Genetic testing for inherited PrCa is usually limited to small gene panels, even though common variants are recognised as harbouring a significant proportion of heritable risk. We have developed a genetic test to identify individuals with a genetic predisposition to PrCa from rare and/or common risk variants, with added potential to inform clinical management of PrCa patients, by detecting targets for personalised treatment, and gather further evidence for candidate genes.

methodsGermline genetic testing was offered to 1095 PrCa patients, as part of a research study, to inform on genetic predisposition and determine eligibility for personalised treatment options. Targeted sequencing of 117 DDR genes and HOXB13 was performed together with genotyping of 130–396 common PrCa risk variants. This test we have called PRODICT. Genetic reports were provided to participants including (A) rare variant status and (B) polygenic risk score (PRS).

resultsPathogenic or likely pathogenic (P/LP) variants were detected in 16.7% of cases, most frequently in MUTYH (2.5%), CHEK2 (2.2%), ATM (1.4%) and BRCA2 (1.3%) and 46.0% of study participants had a PRS in the top quintile of the risk distribution. Univariate analyses of the predominantly European cohort showed that carriers of P/LP variants in PrCa predisposition genes were more likely to be Grade Group ≥ 4 (odds ratio (OR) = 4.57, 95% confidence interval (CI) = 1.33–15.73, p = 0.02) and have metastatic disease (OR = 2.12, 95% CI = 1.09–4.12, p = 0.03), however, once all genes with a P/LP variant were included in the analysis, the associations were not statistically significant. Carriers of a P/LP variant in any DDR gene, were more likely to have a PRS in the bottom quintile of the risk distribution than the top, compared to non-carriers (OR = 2.39, 95% CI = 1.17–4.89, p = 0.02). Overall, based on the PRODICT test, we found that 48.3% of study participants had increased germline genetic predisposition to PrCa.

conclusionsOur single germline genetic test for rare and common risk variants, identifies a significant number of individuals with a genetic predisposition to PrCa and has potential to inform clinical decision making for these patients.

Indexed as

Clinical Decision-MakingGenetic Predisposition to DiseaseGenetic TestingGerm-Line MutationPrecision MedicineProstatic NeoplasmsAgedCheckpoint Kinase 2Genetic Risk ScoreHomeodomain ProteinsHumansMaleMiddle AgedRisk FactorsCheckpoint Kinase 2CHEK2 protein, humanHomeodomain ProteinsHOXB13 protein, humanGenetic testingGermline variantsPolygenic risk scoreProstate cancer

Identifiers

PMID42001130
PMCPMC13224455

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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.