No Association Between Polygenic Risk Scores for Cancer and Development of Radiation Therapy Toxicity.
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ICR Authors
Authors
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
RGC and REQUITE Consortia,
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
RGC and REQUITE Consortia,
Document Type
Journal Article
Date
2022-11-01
Date Accepted
2022-06-26
Abstract
PURPOSE: Our aim was to test whether updated polygenic risk scores (PRS) for susceptibility to cancer affect risk of radiation therapy toxicity. METHODS AND MATERIALS: Analyses included 9,717 patients with breast (n=3,078), prostate (n=5,748) or lung (n=891) cancer from Radiogenomics and REQUITE Consortia cohorts. Patients underwent potentially curative radiation therapy and were assessed prospectively for toxicity. Germline genotyping involved genome-wide single nucleotide polymorphism (SNP) arrays with nontyped SNPs imputed. PRS for each cancer were generated by summing literature-identified cancer susceptibility risk alleles: 352 breast, 136 prostate, and 24 lung. Weighted PRS were generated using log odds ratio (ORs) 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% confidence interval [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 edema (OR, 0.94; 95% CI, 0.92-0.97; P = 1.08 × 10-5). CONCLUSIONS: Patients with increased polygenic predisposition to breast, prostate, or lung cancer can safely undergo radiation therapy with no anticipated excess toxicity risk. Some individual SNPs increase the likelihood of a specific toxicity endpoint, warranting validation in independent cohorts and functional studies to elucidate biologic mechanisms.
Citation
International Journal of Radiation: Oncology - Biology - Physics, 2022, pp. S0360-3016(22)00707-6 -
Source Title
International Journal of Radiation: Oncology - Biology - Physics
Publisher
ELSEVIER SCIENCE INC
ISSN
0360-3016
eISSN
1879-355X
1879-355X
1879-355X