Journal Article

DKFZ-2022-01495

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png No association between polygenic risk scores for cancer and development of radiotherapy toxicity.

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, N. G. ; Summersgill, H. ; Webb, A. ; De Ruysscher, D. ; Seibold, P.DKFZ* ; Chang-Claude, J.DKFZ* ; Talbot, C. J. ; Rattay, T. ; Parliament, M. ; De Ruyck, K. ; Rosenstein, B. S. ; Pharoah, P. D. P. ; Dunning, A. M. ; Vega, A. ; West, C. M. L.

2022
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ijrobp.2022.06.098

Abstract: To test whether updated polygenic risk scores (PRS) for susceptibility to cancer affect risk of radiotherapy toxicity.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.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).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.

Note: 2022 Nov 1;114(3):494-501

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2022

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; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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