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Association of radiation-induced normal tissue toxicity with a high genetic risk for rheumatoid arthritis

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.Primary analysis was performed on 1494 pros...

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Main Authors: McWilliams, Alan (Author) , Marshall, Deborah (Author) , Kerns, Sarah L (Author) , Barnett, Gillian C (Author) , Vega, Ana (Author) , Kapouranis, Thodori (Author) , Aguado Barrera, Miguel E (Author) , Avuzzi, Barbara (Author) , Azria, David (Author) , Chang-Claude, Jenny (Author) , Choudhury, Ananya (Author) , Coedo Costa, Carla (Author) , Dunning, Alison (Author) , Farcy-Jacquet, Marie-Pierre (Author) , Faivre-Finn, Corinne (Author) , Gutiérrez-Enríquez, Sara (Author) , Fuentes-Ríos, Olivia (Author) , Gómez Caamaño, Antonio (Author) , Lambrecht, Maarten (Author) , López Pleguezuelos, Carlos (Author) , Rancati, Tiziana (Author) , Rattay, Tim (Author) , de Ruysscher, Dirk (Author) , Seibold, Petra (Author) , Sperk, Elena (Author) , Talbot, Christopher (Author) , Webb, Adam (Author) , Veldeman, Liv (Author) , Rosenstein, Barry S (Author) , West, Catharine M L (Author)
Format: Article (Journal)
Language:English
Published: May 2025
In: Journal of the National Cancer Institute
Year: 2025, Volume: 117, Issue: 5, Pages: 1018-1026
ISSN:1460-2105
DOI:10.1093/jnci/djae349
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1093/jnci/djae349
Verlag, kostenfrei, Volltext: https://academic.oup.com/jnci/article/117/5/1018/7943498
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Author Notes:Alan McWilliam, PhD, Deborah Marshall, PhD, Sarah L. Kerns, PhD, Gillian C. Barnett, PhD, Ana Vega, PhD, Thodori Kapouranis, PhD, Miguel E. Aguado Barrera, PhD, Barbara Avuzzi , PhD, David Azria, PhD, Jenny Chang-Claude, PhD, Ananya Choudhury, PhD, Carla Coedo Costa, PhD, Alison Dunning, PhD, Marie-Pierre Farcy-Jacquet, PhD, Corinne Faivre-Finn, PhD, Sara Gutiérrez-Enríquez, PhD, Olivia Fuentes-Ríos, PhD, Antonio Gómez Caamaño, PhD, Maarten Lambrecht, PhD, Carlos López Pleguezuelos, PhD, Tiziana Rancati, PhD, Tim Rattay, PhD, Dirk de Ruysscher, PhD, Petra Seibold, PhD, Elena Sperk , PhD, Christopher Talbot, PhD, Adam Webb, PhD, Liv Veldeman, PhD, Barry S. Rosenstein, PhD, Catharine M. L. West, PhD, on behalf of the REQUITE Consortium
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Summary: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.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.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.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.
Item Description:Online veröffentlicht: 6. Januar 2025
Gesehen am 02.06.2025
Physical Description:Online Resource
ISSN:1460-2105
DOI:10.1093/jnci/djae349

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