Polygenic Risk Score-Stratified Cancer Screening: Building the Evidence Base
Abstract
Cancer screening programmes apply one-size-fits-all criteria, assuming homogeneous population risk. Identical protocols may miss cancers in high-risk individuals while overdiagnosing lower-risk groups. PRSs, aggregating effects of cancer-associated variants, offer a pathway toward risk-stratified screening, but their clinical utility across cancer types has not been systematically evaluated. We conducted a systematic review within the Jane2 Network of Expertise EU funded Joint Action, searched PubMed, Web of Science, and Scopus up to March 2026. Studies evaluating PRS-based screening for breast, colorectal, prostate, lung, gastric, and cervical cancer in adults were included, with non-stratified screening as comparators. Outcomes included mortality, life-years gained, QALYs, overdiagnosis, and false positives. Certainty was assessed via GRADE. 25 studies were included, covering breast (10), colorectal (10), prostate (8), lung (3), and gastric cancer (1); no eligible studies addressed cervical cancer. Most were decision-analytic models (22), of which 19 included economic evaluations. PRS-based screening consistently showed favourable directionality: increased deaths averted and QALYs for breast, colorectal, gastric, and lung cancer versus age-based comparators. For prostate cancer, the primary benefit was reduced overdiagnosis rather than mortality improvement. Certainty of evidence was Very Low across all outcomes, driven by serious risk of bias and very serious indirectness, including reliance on EU-ancestry PRSs without local recalibration. PRS-based screening shows consistent but modest potential to improve efficiency across multiple cancer sites, aligning with the WISDOM trial. However, Very Low certainty mandates PRS stratification remains investigational. Priorities include trials with mortality endpoints, ancestry-diverse validation, and equity-sensitive implementation. These findings provide a benchmark for evidence-informed evolution of EU screening.
Key messages: • PRS-stratified screening consistently shows favourable directionality across breast, colorectal, prostate, lung, and gastric cancer, but Very Low certainty of evidence prevents routine implementation.
• This first cross-cancer systematic review of PRS-stratified screening provides a quantitative benchmark for ongoing trials and supports evidence-informed evolution of population screening programmes.
Related
- Healthcare workers and caregivers’ perspectives on access to cancer screening for people with intellectual disabilities as revealed by system dynamics and group model building
- Polygenic and classical risk integration reshapes breast cancer screening recommendations in 9,761 Asian women
- A risk-stratified dynamic screening framework for age-related macular degeneration via a clustering-based partially observable markov decision process
- Rapid Psychosocial Screening Instruments for Cancer Patients: A Scoping Review of Measurement Tools and Psychometric Evidence
- LLM-assisted evidence audit of late-stage cancer incidence as a screening trial endpoint
BibTeX
@article{pascucci2026polygenic,
title = {{Polygenic Risk Score-Stratified Cancer Screening: Building the Evidence Base}},
author = {E Pascucci and N Lentini and A Valz Gris and S Farina and L Russo and L Proto and R Pastorino and S Boccia},
journal = {The European Journal of Public Health},
year = {2026},
month = oct,
doi = {10.1093/eurpub/ckag169.1843},
url = {https://doi.org/10.1093/eurpub/ckag169.1843},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Polygenic Risk Score-Stratified Cancer Screening: Building the Evidence Base
AU - E Pascucci
AU - N Lentini
AU - A Valz Gris
AU - S Farina
AU - L Russo
AU - L Proto
AU - R Pastorino
AU - S Boccia
PY - 2026
DA - 2026/10/01
JO - The European Journal of Public Health
DO - 10.1093/eurpub/ckag169.1843
UR - https://doi.org/10.1093/eurpub/ckag169.1843
AB - Cancer screening programmes apply one-size-fits-all criteria, assuming homogeneous population risk. Identical protocols may miss cancers in high-risk individuals while overdiagnosing lower-risk groups. PRSs, aggregating effects of cancer-associated variants, offer a pathway toward risk-stratified screening, but their clinical utility across cancer types has not been systematically evaluated. We conducted a systematic review within the Jane2 Network of Expertise EU funded Joint Action, searched PubMed, Web of Science, and Scopus up to March 2026. Studies evaluating PRS-based screening for breast, colorectal, prostate, lung, gastric, and cervical cancer in adults were included, with non-stratified screening as comparators. Outcomes included mortality, life-years gained, QALYs, overdiagnosis, and false positives. Certainty was assessed via GRADE. 25 studies were included, covering breast (10), colorectal (10), prostate (8), lung (3), and gastric cancer (1); no eligible studies addressed cervical cancer. Most were decision-analytic models (22), of which 19 included economic evaluations. PRS-based screening consistently showed favourable directionality: increased deaths averted and QALYs for breast, colorectal, gastric, and lung cancer versus age-based comparators. For prostate cancer, the primary benefit was reduced overdiagnosis rather than mortality improvement. Certainty of evidence was Very Low across all outcomes, driven by serious risk of bias and very serious indirectness, including reliance on EU-ancestry PRSs without local recalibration. PRS-based screening shows consistent but modest potential to improve efficiency across multiple cancer sites, aligning with the WISDOM trial. However, Very Low certainty mandates PRS stratification remains investigational. Priorities include trials with mortality endpoints, ancestry-diverse validation, and equity-sensitive implementation. These findings provide a benchmark for evidence-informed evolution of EU screening. Key messages: • PRS-stratified screening consistently shows favourable directionality across breast, colorectal, prostate, lung, and gastric cancer, but Very Low certainty of evidence prevents routine implementation. • This first cross-cancer systematic review of PRS-stratified screening provides a quantitative benchmark for ongoing trials and supports evidence-informed evolution of population screening programmes.
SN - 1101-1262
SN - 1464-360X
ER -