# Polygenic risk score (PRS)

Source: https://onco.cc/terms/polygenic-risk-score/  
OnCo record `polygenic-risk-score` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A single number adding up hundreds of common, individually tiny genetic differences to say whether a man's inherited risk of prostate cancer is above or below average. It is not a test for a faulty gene like BRCA2, and it says nothing about how aggressive a cancer would be.

## Summary

A polygenic risk score is the weighted sum of the risk alleles a person carries across a set of common single nucleotide polymorphisms identified by genome-wide association studies, each of which shifts risk by a fraction of a percent. It is a population ranking device: it places a man in a percentile of inherited susceptibility. It is categorically different from a germline test for a rare high-penetrance variant such as BRCA2 or a mismatch repair gene, which names a single fault with a large effect and consequences for relatives.

Prostate cancer has the best-developed score of any common cancer, and the biggest ancestry problem. Conti, Haiman and Eeles ran a multi-ancestry meta-analysis of 107,247 cases and 127,006 controls, identified 86 new risk variants for a total of 269, and built a score from them. The top decile carried odds ratios from 5.06 (95 percent confidence interval 4.84 to 5.29) in men of European ancestry to 3.74 (3.36 to 4.17) in men of African ancestry, and the mean score was 2.18 times higher in men of African ancestry (2.14 to 2.22) and 0.73 times that of European ancestry in men of East Asian ancestry (0.71 to 0.76). The discovery data were largely European, which is why the score discriminates least well in the group with the highest mean risk.

The United Kingdom has tested it prospectively. BARCODE1 recruited men aged 55 to 69 through primary care, derived a score from 130 variants using saliva DNA, and invited those at or above the 90th percentile for multiparametric magnetic resonance imaging and transperineal biopsy irrespective of prostate-specific antigen. Of 40,292 invited, 6,393 had a score calculated, 745 (11.7 percent) were in the top decile and 468 were screened; prostate cancer was found in 187 (40.0 percent), of whom 103 had disease of intermediate risk or higher by 2024 NCCN criteria, and 74 of those 103 would not have been detected by the current United Kingdom pathway of raised prostate-specific antigen followed by magnetic resonance imaging. The trial had no comparator arm, which is the basis of the main criticism: standardised to 10,000 men tested, Sud and Vickers calculated that BARCODE1 biopsied more men (704 against 386 and 338), found more low-grade cancers (126 against 103 and 41) and found fewer high-grade cancers (155 against 178 and 165) than the contemporaneous Goteborg-2 and ProScreen trials, which risk-stratify with magnetic resonance imaging and blood markers. The open question is therefore not whether a score can find cancer but whether it finds the cancer that matters, and the current evidence is that it does not preferentially find aggressive disease.

## Fields

- Kind: Term
- Last checked: 2026-09-25
- Also known as: PRS; polygenic score; genetic risk score; GRS; SNP risk score; polygenic risk score prostate
- Tags: gu; prostate-glossary

## Notes

- It ranks risk of getting the disease, not risk of dying of it. Nothing in a polygenic risk score distinguishes a grade group 1 cancer that will sit quietly for twenty years from a grade group 5 cancer, which is why a screening programme selected by score alone will find a great deal of low-grade disease. That is the substance of the criticism of BARCODE1 and the reason its result is not a recommendation.
- It is not a germline test in the clinical sense. A polygenic risk score carries no implication for relatives that would trigger cascade testing, no eligibility for a PARP inhibitor and no change of surveillance in the way a pathogenic BRCA2 variant does. A man may have both tests and they answer different questions.
- Ancestry is not a technical footnote here. A score built mostly in European-ancestry cohorts performs worse in men of African ancestry, who carry the highest mean score and the highest incidence, so a programme that adopts the score without fixing the discovery imbalance under-serves the group with most to gain.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Polygenic_score
- Conti et al., Nature Genetics 2021: trans-ancestry genome-wide association meta-analysis of prostate cancer: https://doi.org/10.1038/s41588-020-00748-0
- McHugh et al., New England Journal of Medicine 2025 (BARCODE1): assessment of a polygenic risk score in screening for prostate cancer: https://doi.org/10.1056/nejmoa2407934
- Benafif et al., BJU International 2022: the BARCODE1 pilot, a feasibility study of using germline single nucleotide polymorphisms to target prostate cancer screening: https://doi.org/10.1111/bju.15535
- Sud, McNeill and Vickers, European Urology Oncology 2026: comparison of results from the BARCODE1 study and contemporary prostate cancer screening trials: https://doi.org/10.1016/j.euo.2025.12.013
- Auvinen et al., JAMA 2024 (ProScreen): prostate cancer screening with PSA, kallikrein panel and MRI: https://doi.org/10.1001/jama.2024.3841

## Connected records

- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [MRI](https://onco.cc/technologies/mri/), [Polygenic risk scores for cancer](https://onco.cc/technologies/polygenic-risk-scores/), [PSA and MRI-first prostate cancer screening](https://onco.cc/technologies/prostate-screening-psa-mri/)
- key papers: [Association of Black race with prostate cancer-specific and other-cause mortality](https://onco.cc/key-papers/paper-dess-black-race-prostate-mortality-jama-oncol-2019/), [Prostate Cancer Screening with PSA and MRI Followed by Targeted Biopsy Only](https://onco.cc/key-papers/paper-goteborg-2-n-engl-j-med-2022/), [Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction](https://onco.cc/key-papers/paper-conti-trans-ancestry-gwas-prostate-nat-genet-2021/)
- ideas: [MRI-first prostate screening with genetic pre-selection](https://onco.cc/ideas/idea-prev-mri-first-prostate-screening-prs/), [Use a polygenic risk score to set when screening starts](https://onco.cc/ideas/idea-prev-prs-screening-start-age/)
- cancers: [Localised prostate cancer, high and very high risk](https://onco.cc/cancers/prostate-high-risk/), [Localised prostate cancer, intermediate risk](https://onco.cc/cancers/prostate-intermediate-risk/), [Localised prostate cancer, very low and low risk](https://onco.cc/cancers/prostate-low-risk/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Early Detection & Screening](https://onco.cc/fronts/early-detection/), [Prevention & Risk](https://onco.cc/fronts/prevention/)
- terms: [Lead time, and lead-time bias](https://onco.cc/terms/lead-time-bias/), [Number needed to screen (and number needed to diagnose)](https://onco.cc/terms/number-needed-to-screen/), [Overdiagnosis](https://onco.cc/terms/overdiagnosis/), [PSA (prostate-specific antigen)](https://onco.cc/terms/psa/), [Screening](https://onco.cc/terms/screening/)
- bottlenecks: [Inherited risk is mostly unidentified](https://onco.cc/bottlenecks/b-hereditary-risk/), [Overdiagnosis and false alarms](https://onco.cc/bottlenecks/b-overdiagnosis/), [The hardest cancers are found late](https://onco.cc/bottlenecks/b-early-detection/), [Trials do not represent the people who get cancer](https://onco.cc/bottlenecks/b-trial-diversity/)

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