# Polygenic risk scores for cancer

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

## TL;DR

A score built from hundreds of common gene variants that says whether your inherited risk of a cancer is higher or lower than average, now being tested as a way to decide who is screened and how often.

## Summary

Polygenic risk scores sum the small effects of hundreds to millions of common variants. The 313-variant breast cancer score (Mavaddat et al., 2019) stratifies women across a several-fold range of lifetime risk and is included in the CanRisk (BOADICEA) model used in UK clinics; prostate cancer scores identify men in the top decile of risk, and the BARCODE1 study (2025) offered MRI and biopsy to such men regardless of PSA and found a high yield of clinically significant cancer. Risk-based screening trials, WISDOM in the US (NCT02620852) and MyPeBS in Europe, are testing whether tailoring mammography by risk, including polygenic risk, is as safe as age-based screening, and the UK TRANSFORM prostate trial includes a genetic testing arm. The main limitations are poor transferability to people of non-European ancestry, modest discrimination compared with a pathogenic BRCA variant, and the absence so far of proof that acting on a score improves outcomes.

## Fields

- Kind: Technology
- Status: emerging
- Last checked: 2026-09-10
- Principle: Genome-wide association study effect sizes are summed across an individual's genotyped variants, then combined with age, family history and other risk factors in an absolute-risk model.
- Strengths: Cheap, once-in-a-lifetime genotyping; Refines who benefits from earlier or more intensive screening
- Limitations: Ancestry bias in training data; Modest per-person discrimination; Clinical utility unproven

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Polygenic_score
- Mavaddat et al., 313-SNP breast cancer PRS (AJHG 2019): https://doi.org/10.1016/j.ajhg.2018.11.002
- ClinicalTrials.gov NCT02620852: https://clinicaltrials.gov/study/NCT02620852

## Connected records

- terms: [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Polygenic risk score (PRS)](https://onco.cc/terms/polygenic-risk-score/), [Screening](https://onco.cc/terms/screening/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- fronts: [AI & Computation](https://onco.cc/fronts/ai-computation/), [Early Detection & Screening](https://onco.cc/fronts/early-detection/), [Prevention & Risk](https://onco.cc/fronts/prevention/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Mammography & tomosynthesis](https://onco.cc/technologies/mammography/), [PSA and MRI-first prostate cancer screening](https://onco.cc/technologies/prostate-screening-psa-mri/)
- key papers: [Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes](https://onco.cc/key-papers/paper-mavaddat-am-j-hum-genet/)
- roadmaps: [Cancer prevention roadmap: tobacco control and vaccines → biomarker-guided chemoprevention → interception in carriers](https://onco.cc/roadmaps/prevention-roadmap/)
- trials: [WISDOM (Women Informed to Screen Depending on Measures of Risk)](https://onco.cc/trials/wisdom-trial/)

---
JSON: https://onco.cc/api/v1/entities/polygenic-risk-scores.json