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

REQUITE consortium; Alan Mcwilliam; Deborah Marshall; Sarah L Kerns; Gillian C Barnett; Ana Vega; Thodori Kapouranis; Miguel E Aguado Barrera; Barbara Avuzzi; David Azria; Jenny Chang-Claude; Ananya Choudhury; Carla Coedo Costa; Alison Dunning; Marie-Pierre Farcy-Jacquet; Corinne Faivre-Finn; Sara Gutiérrez-Enríquez; Olivia Fuentes Río; Antonio Gómez Caamaño; Maarten Lambrecht; Carlos López Pleguezuelos; Tiziana Rancati; Tim Rattay; Dirk De Ruysscher; Petra Seibold; Elena Sperk; Christopher Talbot; Adam Webb; Liv Veldeman; Barry S Rosenstein; Catharine M L West

doi:10.1093/jnci/djae349

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

REQUITE consortium, Alan Mcwilliam, Deborah Marshall, Sarah L Kerns, Gillian C Barnett, Ana Vega, Thodori Kapouranis, Miguel E Aguado Barrera, Barbara Avuzzi, David Azria, Jenny Chang-Claude, Ananya Choudhury, Carla Coedo Costa, Alison Dunning, Marie-Pierre Farcy-Jacquet, Corinne Faivre-Finn, Sara Gutiérrez-Enríquez, Olivia Fuentes Río, Antonio Gómez Caamaño, Maarten LambrechtCarlos López Pleguezuelos, Tiziana Rancati, Tim Rattay, Dirk De Ruysscher, Petra Seibold, Elena Sperk, Christopher Talbot, Adam Webb, Liv Veldeman, Barry S Rosenstein, Catharine M L West

Division of Cancer Sciences (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

PURPOSE: Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesised that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) 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 RT toxicity in the REQUITE 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 PRS to be calculated using 101 RA risk variants. PRS was analysed as a continuous variable and with >90th percentile cut-off. Associations with acute and late standardised total average toxicity (STAT) scores and individual toxicity end-points were analysed in multivariable models with preselected adjustment variables.

RESULTS: Increasing PRS for RA did not increase the risk of acute or late STAT in any cohort. There was an increased risk of late oesophagitis 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 significantly associated with PRS for the prostate or breast cohorts. No 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.

Original language	English
Article number	djae349
Journal	Journal of the National Cancer Institute
Early online date	6 Jan 2025
DOIs	https://doi.org/10.1093/jnci/djae349
Publication status	E-pub ahead of print - 6 Jan 2025

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10.1093/jnci/djae349Licence: CC BY

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REQUITE consortium, Mcwilliam, A., Marshall, D., Kerns, S. L., Barnett, G. C., Vega, A., Kapouranis, T., Aguado Barrera, M. E., Avuzzi, B., Azria, D., Chang-Claude, J., Choudhury, A., Coedo Costa, C., Dunning, A., Farcy-Jacquet, M.-P., Faivre-Finn, C., Gutiérrez-Enríquez, S., Fuentes Río, O., Gómez Caamaño, A., ... West, C. M. L. (2025). Association of radiation-induced normal tissue toxicity with a high genetic risk for rheumatoid arthritis. Journal of the National Cancer Institute, Article djae349. Advance online publication. https://doi.org/10.1093/jnci/djae349

@article{766a4cce19214449832e841e2b13bbf2,

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

abstract = "PURPOSE: Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesised that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) 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 RT toxicity in the REQUITE 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 PRS to be calculated using 101 RA risk variants. PRS was analysed as a continuous variable and with >90th percentile cut-off. Associations with acute and late standardised total average toxicity (STAT) scores and individual toxicity end-points were analysed in multivariable models with preselected adjustment variables.RESULTS: Increasing PRS for RA did not increase the risk of acute or late STAT in any cohort. There was an increased risk of late oesophagitis 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 significantly associated with PRS for the prostate or breast cohorts. No 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.",

author = "{REQUITE consortium} and Alan Mcwilliam and Deborah Marshall and Kerns, {Sarah L} and Barnett, {Gillian C} and Ana Vega and Thodori Kapouranis and {Aguado Barrera}, {Miguel E} and Barbara Avuzzi and David Azria and Jenny Chang-Claude and Ananya Choudhury and {Coedo Costa}, Carla and Alison Dunning and Marie-Pierre Farcy-Jacquet and Corinne Faivre-Finn and Sara Guti{\'e}rrez-Enr{\'i}quez and {Fuentes R{\'i}o}, Olivia and {G{\'o}mez Caama{\~n}o}, Antonio and Maarten Lambrecht and {L{\'o}pez Pleguezuelos}, Carlos and Tiziana Rancati and Tim Rattay and {De Ruysscher}, Dirk and Petra Seibold and Elena Sperk and Christopher Talbot and Adam Webb and Liv Veldeman and Rosenstein, {Barry S} and West, {Catharine M L}",

note = "{\textcopyright} The Author(s) 2025. Published by Oxford University Press.",

year = "2025",

month = jan,

day = "6",

doi = "10.1093/jnci/djae349",

language = "English",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

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REQUITE consortium, Mcwilliam, A, Marshall, D, Kerns, SL, Barnett, GC, Vega, A, Kapouranis, T, Aguado Barrera, ME, Avuzzi, B, Azria, D, Chang-Claude, J, Choudhury, A, Coedo Costa, C, Dunning, A, Farcy-Jacquet, M-P, Faivre-Finn, C, Gutiérrez-Enríquez, S, Fuentes Río, O, Gómez Caamaño, A, Lambrecht, M, López Pleguezuelos, C, Rancati, T, Rattay, T, De Ruysscher, D, Seibold, P, Sperk, E, Talbot, C, Webb, A, Veldeman, L, Rosenstein, BS & West, CML 2025, 'Association of radiation-induced normal tissue toxicity with a high genetic risk for rheumatoid arthritis', Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/djae349

TY - JOUR

T1 - Association of radiation-induced normal tissue toxicity with a high genetic risk for rheumatoid arthritis

AU - REQUITE consortium

AU - Mcwilliam, Alan

AU - Marshall, Deborah

AU - Kerns, Sarah L

AU - Barnett, Gillian C

AU - Vega, Ana

AU - Kapouranis, Thodori

AU - Aguado Barrera, Miguel E

AU - Avuzzi, Barbara

AU - Azria, David

AU - Chang-Claude, Jenny

AU - Choudhury, Ananya

AU - Coedo Costa, Carla

AU - Dunning, Alison

AU - Farcy-Jacquet, Marie-Pierre

AU - Faivre-Finn, Corinne

AU - Gutiérrez-Enríquez, Sara

AU - Fuentes Río, Olivia

AU - Gómez Caamaño, Antonio

AU - Lambrecht, Maarten

AU - López Pleguezuelos, Carlos

AU - Rancati, Tiziana

AU - Rattay, Tim

AU - De Ruysscher, Dirk

AU - Seibold, Petra

AU - Sperk, Elena

AU - Talbot, Christopher

AU - Webb, Adam

AU - Veldeman, Liv

AU - Rosenstein, Barry S

AU - West, Catharine M L

PY - 2025/1/6

Y1 - 2025/1/6

N2 - PURPOSE: Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesised that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) 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 RT toxicity in the REQUITE 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 PRS to be calculated using 101 RA risk variants. PRS was analysed as a continuous variable and with >90th percentile cut-off. Associations with acute and late standardised total average toxicity (STAT) scores and individual toxicity end-points were analysed in multivariable models with preselected adjustment variables.RESULTS: Increasing PRS for RA did not increase the risk of acute or late STAT in any cohort. There was an increased risk of late oesophagitis 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 significantly associated with PRS for the prostate or breast cohorts. No 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.

AB - PURPOSE: Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesised that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) 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 RT toxicity in the REQUITE 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 PRS to be calculated using 101 RA risk variants. PRS was analysed as a continuous variable and with >90th percentile cut-off. Associations with acute and late standardised total average toxicity (STAT) scores and individual toxicity end-points were analysed in multivariable models with preselected adjustment variables.RESULTS: Increasing PRS for RA did not increase the risk of acute or late STAT in any cohort. There was an increased risk of late oesophagitis 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 significantly associated with PRS for the prostate or breast cohorts. No 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.

U2 - 10.1093/jnci/djae349

DO - 10.1093/jnci/djae349

M3 - Article

C2 - 39761002

SN - 0027-8874

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

M1 - djae349

ER -

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

Abstract

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