Faculty Collaboration Database

No Association Between Polygenic Risk Scores for Cancer and Development of Radiation Therapy Toxicity. Int J Radiat Oncol Biol Phys 2022 Nov 01;114(3):494-501

Date

07/16/2022

Pubmed ID

35840111

DOI

10.1016/j.ijrobp.2022.06.098

Scopus ID

2-s2.0-85138029152 (requires institutional sign-in at Scopus site)   2 Citations

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.

Author List

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

Author

Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Biological Products
Breast Neoplasms
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Polymorphism, Single Nucleotide
Prostatic Neoplasms
Radiation Injuries
Risk Factors