ArticleRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2021
Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity.
Article in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 32 citations in OpenAlex.
- Predictive Factors for Acute and Late Genitourinary and Gastrointestinal Toxicity Following Modern Radiotherapy for Prostate Cancer: A Narrative Review of Clinical, Dosimetric, Immunological, and Genetic Determinants.Life (Basel, Switzerland) · 2026Review
- WDCN: a comprehensive neural network based approach for estimating breast cancer risk.Briefings in bioinformatics · 2026Article
- Novel method for risk stratification of radiation-induced breast fibrosis: subgroup hypothesis verified by machine learning.NPJ breast cancer · 2026Article
- From Cellular Radiosensitivity to Precision Radiotherapy: Integrating Functional Assays, Genomics, and Clinical Modeling.Cancers · 2026Review
- Voxel-Based Dose-Toxicity Modeling for Predicting Post-Radiotherapy Toxicity: A Critical Perspective.Journal of clinical medicine · 2025Article
- Integrating genetic polymorphisms and clinical data to develop predictive models for skin toxicity in breast cancer radiation therapy.Breast (Edinburgh, Scotland) · 2025Article
- A Polygenic Risk Score for Late Bladder Toxicity Following Radiotherapy for Non-Metastatic Prostate Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Article
- Towards Personalized Radiotherapy in Pelvic Cancer: Patient-Related Risk Factors for Late Radiation Toxicity.Current oncology (Toronto, Ont.) · 2025Review
- ApplyPolygenicScore: An R package for applying polygenic risk score models.Genetics in medicine open · 2025Article
- Data Science Opportunities To Improve Radiotherapy Planning and Clinical Decision Making.Seminars in radiation oncology · 2024Review
- Epistatic Features and Machine Learning Improve Alzheimer's Disease Risk Prediction Over Polygenic Risk Scores.Journal of Alzheimer's disease : JAD · 2024Article
- Heterogeneity in precision oncology.Cambridge prisms. Precision medicine · 2024Review
- Transfer learning with false negative control improves polygenic risk prediction.PLoS genetics · 2023Article
- Longitudinal cosmetic outcome after planned IORT boost with low kV X-rays-monocentric results from the TARGIT BQR registry.Translational cancer research · 2023Article
- Article
- The Normal, the Radiosensitive, and the Ataxic in the Era of Precision Radiotherapy: A Narrative Review.Cancers · 2022Review
- Article
Corrections and comments
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Authors and funding
44 authors at 20 institutions in 8 countries.
Funding
Abstract
aimTo identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi). MATERIALS AND
methodsAnalysis included the REQUITE PCa cohort that received external beam RT and was followed for 2 years. Late toxicity endpoints were: rectal bleeding, urinary frequency, haematuria, nocturia, decreased urinary stream. Among 43 literature-identified SNPs, the 30% most strongly associated with each toxicity were tested. SNP-SNP combinations (named SNP-allele sets) seen in ≥10% of the cohort were condensed into risk (RS) and protection (PS) scores, respectively indicating increased or decreased toxicity risk. Performance of RS and PS was evaluated by logistic regression. RS and PS were then combined into a single PRSi evaluated by area under the receiver operating characteristic curve (AUC).
resultsAmong 1,387 analysed patients, toxicity rates were 11.7% (rectal bleeding), 4.0% (urinary frequency), 5.5% (haematuria), 7.8% (nocturia) and 17.1% (decreased urinary stream). RS and PS combined 8 to 15 different SNP-allele sets, depending on the toxicity endpoint. Distributions of PRSi differed significantly in patients with/without toxicity with AUCs ranging from 0.61 to 0.78. PRSi was better than the classical summed PRS, particularly for the urinary frequency, haematuria and decreased urinary stream endpoints.
conclusionsOur method incorporates SNP-SNP interactions when calculating PRS for radiotherapy toxicity. Our approach is better than classical summation in discriminating patients with toxicity and should enable incorporating genetic information to improve normal tissue complication probability models.
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