| Added by | JPPOUGET |
|---|---|
| Group name | EquipeJPP |
| Item Type | Journal Article |
| Title | Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity |
| Creator | Franco et al. |
| Author | Nicola Rares Franco |
| Author | Michela Carlotta Massi |
| Author | Francesca Ieva |
| Author | Andrea Manzoni |
| Author | Anna Maria Paganoni |
| Author | Paolo Zunino |
| Author | Liv Veldeman |
| Author | Piet Ost |
| Author | Valérie Fonteyne |
| Author | Christopher J. Talbot |
| Author | Tim Rattay |
| Author | Adam Webb |
| Author | Kerstie Johnson |
| Author | Maarten Lambrecht |
| Author | Karin Haustermans |
| Author | Gert De Meerleer |
| Author | Ben Vanneste |
| Author | Evert Van Limbergen |
| Author | Ananya Choudhury |
| Author | Rebecca M. Elliott |
| Author | Elena Sperk |
| Author | Marlon R. Veldwijk |
| Author | Carsten Herskind |
| Author | Barbara Avuzzi |
| Author | Barbara Noris Chiorda |
| Author | Riccardo Valdagni |
| Author | David Azria |
| Author | Marie-Pierre Farcy-Jacquet |
| Author | Muriel Brengues |
| Author | Barry S. Rosenstein |
| Author | Richard G. Stock |
| Author | Ana Vega |
| Author | Miguel E. Aguado-Barrera |
| Author | Paloma Sosa-Fajardo |
| Author | Alison M. Dunning |
| Author | Laura Fachal |
| Author | Sarah L. Kerns |
| Author | Debbie Payne |
| Author | Jenny Chang-Claude |
| Author | Petra Seibold |
| Author | Catharine M. L. West |
| Author | Tiziana Rancati |
| Abstract | AIM: To 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 METHODS: Analysis 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). RESULTS: Among 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. CONCLUSIONS: Our 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. |
| Publication | Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology |
| Volume | 159 |
| Pages | 241-248 |
| Date | 2021-06 |
| Journal Abbr | Radiother Oncol |
| Language | eng |
| DOI | 10.1016/j.radonc.2021.03.024 |
| ISSN | 1879-0887 |
| Library Catalog | PubMed |
| Extra | PMID: 33838170 PMCID: PMC8754257 |
| Tags | Area Under Curve, Epistasis, Genetic risk factors, Humans, Late toxicity, Male, original, Polymorphism, Single Nucleotide, Prostate cancer, Prostatic Neoplasms, Radiation Injuries, Radiotherapy, Risk Factors, SNPs |
| Date Added | 2023/11/23 - 12:48:35 |
| Date Modified | 2024/12/15 - 12:07:47 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
