TY - JOUR
T1 - No Association Between Polygenic Risk Scores for Cancer and Development of Radiation Therapy Toxicity
AU - Barnett, Gillian C
AU - Kerns, Sarah L
AU - Dorling, Leila
AU - Fachal, Laura
AU - Aguado-Barrera, Miguel E
AU - Martínez-Calvo, Laura
AU - Jandu, Harkeran K
AU - Welsh, Ceilidh
AU - Tyrer, Jonathan
AU - Coles, Charlotte E
AU - Haviland, Joanne S
AU - Parker, Christopher
AU - Gómez-Caamaño, Antonio
AU - Calvo-Crespo, Patricia
AU - Sosa-Fajardo, Paloma
AU - Burnet, Neil G
AU - Summersgill, Holly
AU - Webb, Adam
AU - De Ruysscher, Dirk
AU - Seibold, Petra
AU - Chang-Claude, Jenny
AU - Talbot, Christopher J
AU - Rattay, Tim
AU - Parliament, Matthew
AU - De Ruyck, Kim
AU - Rosenstein, Barry S
AU - Pharoah, Paul D P
AU - Dunning, Alison M
AU - Vega, Ana
AU - West, Catharine M L
N1 - Copyright © 2022. Published by Elsevier Inc.
PY - 2022/11/1
Y1 - 2022/11/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.ijrobp.2022.06.098
DO - 10.1016/j.ijrobp.2022.06.098
M3 - Article
C2 - 35840111
SN - 0360-3016
VL - 114
SP - 494
EP - 501
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 3
ER -