No association between polygenic risk scores for cancer and development of radiotherapy toxicity.
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Date
2022-07-12ICR Author
Author
Barnett, GC
Kerns, SL
Dorling, L
Fachal, L
Aguado-Barrera, ME
Martínez-Calvo, L
Jandu, HK
Welsh, C
Tyrer, J
Coles, CE
Haviland, JS
Parker, C
Gómez-Caamaño, A
Calvo-Crespo, P
Sosa-Fajardo, P
Burnet, NG
Summersgill, H
Webb, A
De Ruysscher, D
Seibold, P
Chang-Claude, J
Talbot, CJ
Rattay, T
Parliament, M
De Ruyck, K
Rosenstein, BS
Pharoah, PDP
Dunning, AM
Vega, A
West, CML
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Language
eng
Date accepted
2022-06-26
License start date
2022-07-12
Citation
International Journal of Radiation: Oncology - Biology - Physics, 2022, pp. S0360-3016(22)00707-6 -
Publisher
Elsevier BV