Sistema de Salut de Catalunya
Institut Català de la Salut
[McWilliam A] Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. The Christie NHS Foundation Trust, Manchester, United Kingdom. [Marshall D] Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United States. [Kerns SL] Medical College of Wisconsin, Milwaukee, WI, United States. [Barnett GC] Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. [Vega A] Fundación Pública Galega de Medicina Xenómica (FPGMX), Santiago de Compostela, Spain. Biomedical Network on Rare Diseases (CIBERER), Spain. [Kapouranis T] Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United States. [Gutiérrez-Enríquez S] Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-07-10T06:43:34Z
2025-07-10T06:43:34Z
2025-05
Toxicity; Radiation; Rheumatoid arthritis
Toxicidad; Radiación; Artritis reumatoide
Toxicitat; Radiació; Artritis reumatoide
Background Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesized that patients with a high polygenic risk score for RA will have an increased risk of radiotherapy toxicity given the involvement of DNA repair. Methods Primary analysis was performed on 1494 prostate cancer, 483 lung cancer, and 1820 breast cancer patients assessed for development of radiotherapy toxicity in the REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) study. Validation cohorts were available from the Radiogenomics Consortium. All patients had undergone curative-intent radiotherapy and were assessed prospectively for toxicity. Germline genomic data was available for all patients, allowing a polygenic risk score to be calculated using 101 RA risk variants. Polygenic risk score was analyzed as a continuous variable and with a more than 90th percentile cutoff. Associations with acute and late standardized total average toxicity (STAT) scores and individual toxicity endpoints were analyzed in multivariable models with preselected adjustment variables. Results Increasing polygenic risk score for RA did not increase the risk of STAT-acute or STAT-late in any cohort. There was an increased risk of late esophagitis in the lung cancer cohort (coefficient = 0.018, P = .01), however this was not validated (P = .79). No individual acute or late toxicity endpoints were statistically significantly associated with polygenic risk score for the prostate or breast cohorts. No statistically significant results were found in the validation cohorts in multivariable models. Conclusions Patients with a high genetic risk for RA do not show increased levels of toxicity after radiotherapy suggesting treatment planning does not need to be modified for such patients.
Article
Published version
English
Càncer - Radioteràpia - Complicacions; Artritis reumatoide - Aspectes genètics; Artritis reumatoide - Factors de risc; DISEASES::Musculoskeletal Diseases::Joint Diseases::Arthritis::Arthritis, Rheumatoid; DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease; DISEASES::Neoplasms; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Radiotherapy; Other subheadings::Other subheadings::Other subheadings::/adverse effects; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors; ENFERMEDADES::enfermedades musculoesqueléticas::artropatías::artritis::artritis reumatoide; ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::susceptibilidad a enfermedades::predisposición genética a la enfermedad; ENFERMEDADES::neoplasias; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::radioterapia; Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo
Oxford University Press
JNCI: Journal of the National Cancer Institute;117(5)
https://doi.org/10.1093/jnci/djae349
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
