dc.contributor.author | Barnett, GC | |
dc.contributor.author | Kerns, SL | |
dc.contributor.author | Dorling, L | |
dc.contributor.author | Fachal, L | |
dc.contributor.author | Aguado-Barrera, ME | |
dc.contributor.author | Martínez-Calvo, L | |
dc.contributor.author | Jandu, HK | |
dc.contributor.author | Welsh, C | |
dc.contributor.author | Tyrer, J | |
dc.contributor.author | Coles, CE | |
dc.contributor.author | Haviland, JS | |
dc.contributor.author | Parker, C | |
dc.contributor.author | Gómez-Caamaño, A | |
dc.contributor.author | Calvo-Crespo, P | |
dc.contributor.author | Sosa-Fajardo, P | |
dc.contributor.author | Burnet, NG | |
dc.contributor.author | Summersgill, H | |
dc.contributor.author | Webb, A | |
dc.contributor.author | De Ruysscher, D | |
dc.contributor.author | Seibold, P | |
dc.contributor.author | Chang-Claude, J | |
dc.contributor.author | Talbot, CJ | |
dc.contributor.author | Rattay, T | |
dc.contributor.author | Parliament, M | |
dc.contributor.author | De Ruyck, K | |
dc.contributor.author | Rosenstein, BS | |
dc.contributor.author | Pharoah, PDP | |
dc.contributor.author | Dunning, AM | |
dc.contributor.author | Vega, A | |
dc.contributor.author | West, CML | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-09-27T10:13:38Z | |
dc.date.available | 2022-09-27T10:13:38Z | |
dc.date.issued | 2022-07-12 | |
dc.identifier | S0360-3016(22)00707-6 | |
dc.identifier.citation | International Journal of Radiation: Oncology - Biology - Physics, 2022, pp. S0360-3016(22)00707-6 - | en_US |
dc.identifier.issn | 0360-3016 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5503 | |
dc.identifier.eissn | 1879-355X | |
dc.identifier.eissn | 1879-355X | |
dc.identifier.doi | 10.1016/j.ijrobp.2022.06.098 | |
dc.description.abstract | PURPOSE: To test whether updated polygenic risk scores (PRS) for susceptibility to cancer affect risk of radiotherapy toxicity. EXPERIMENTAL DESIGN: Analyses included 9,717 patients with breast (n=3,078), prostate (n=5,748) or lung (n=891) cancer from XXXX and XXXX Consortia cohorts. Patients underwent potentially curative radiotherapy and were assessed prospectively for toxicity. Germline genotyping involved genome-wide single nucleotide polymorphism (SNP) arrays with non-typed SNPs imputed. PRS for each cancer were generated by summing literature-identified cancer susceptibility risk alleles: 352 breast, 136 prostate, 24 lung. Weighted PRS were generated using log odds ratios for cancer susceptibility. Standardized total average toxicity (STAT) scores at 2 and 5 years (breast, prostate) or 6 to 12 months (lung) quantified toxicity. Primary analysis tested late STAT, secondary analyses investigated acute STAT, and individual endpoints and SNPs using multivariable regression. RESULTS: Increasing PRS did not increase risk of late toxicity in patients with breast (OR 1.000, 95%CI 0.997-1.002), prostate (OR 0.99, 95%CI 0.98-1.00; weighted PRS OR 0.93, 95%CI 0.83-1.03) or lung (OR 0.93, 95%CI 0.87-1.00; weighted PRS OR 0.68, 95%CI 0.45-1.03) cancer. Similar results were seen for acute toxicity. Secondary analyses identified rs138944387 associated with breast pain (OR=3.05; 95%CI 1.86- 5.01; P=1.09 × 10-5) and rs17513613 with breast oedema (OR=0.94; 95%CI 0.92- 0.97; P=1.08 × 1 0-5). CONCLUSIONS: Patients with increased polygenic predisposition to breast, prostate or lung cancer can safely undergo radiotherapy with no anticipated excess toxicity risk. Some individual SNPs increase likelihood of a specific toxicity endpoint warranting validation in independent cohorts and functional studies to elucidate biologic mechanisms. | |
dc.format | Print-Electronic | |
dc.format.extent | S0360-3016(22)00707-6 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | Elsevier BV | en_US |
dc.relation.ispartof | International Journal of Radiation: Oncology - Biology - Physics | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.title | No association between polygenic risk scores for cancer and development of radiotherapy toxicity. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-06-26 | |
dc.date.updated | 2022-09-27T10:13:05Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1016/j.ijrobp.2022.06.098 | en_US |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
rioxxterms.licenseref.startdate | 2022-07-12 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35840111 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.ijrobp.2022.06.098 | |
dc.contributor.icrauthor | Parker, Chris | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Chris Lord) on 2022-09-27. Deposit type is initial. No. of files: 1. Files: PIIS0360301622007076.pdf | |