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    No association between polygenic risk scores for cancer and development of radiotherapy toxicity

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    Authors
    Barnett, G. C.
    Kerns, S. L.
    Dorling, L.
    Fachal, L.
    Aguado-Barrera, M. E.
    Martínez-Calvo, L.
    Jandu, H. K.
    Welsh, C.
    Tyrer, J.
    Coles, C. E.
    Haviland, J. S.
    Parker, C.
    Gómez-Caamaño, A.
    Calvo-Crespo, P.
    Sosa-Fajardo, P.
    Burnet, Neil G
    Summersgill, Holly
    Webb, A.
    De Ruysscher, D.
    Seibold, P.
    Chang-Claude, J.
    Talbot, C. J.
    Rattay, T.
    Parliament, M.
    De Ruyck, K.
    Rosenstein, B. S.
    Pharoah, P. D. P.
    Dunning, A. M.
    Vega, A.
    West, Catharine M L
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    Affiliation
    Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, CB2 0QQ, UK
    Issue Date
    2022
    
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    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.
    Citation
    Barnett GC, Kerns SL, Dorling L, Fachal L, Aguado-Barrera ME, Martínez-Calvo L, et al. No association between polygenic risk scores for cancer and development of radiotherapy toxicity. International journal of radiation oncology, biology, physics. 2022 Jul 12. PubMed PMID: 35840111. Epub 2022/07/16. eng.
    Journal
    International Journal of Radiation Oncology Biology Physics
    URI
    http://hdl.handle.net/10541/625431
    DOI
    10.1016/j.ijrobp.2022.06.098
    PubMed ID
    35840111
    Additional Links
    https://dx.doi.org/10.1016/j.ijrobp.2022.06.098
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ijrobp.2022.06.098
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