Circadian genotypes in PER3 and time of prostate cancer radiotherapy interact to affect risk of late side-effects.

Authors

Adam J Webb, Emily Harper, Tim Rattay, Miguel E Aguado-Barrera, Barbara Avuzzi, Renée Bultijnck, Ananya Choudhury, Dirk K De Ruysscher, Olivia Fuentes-Ríos, Sara Gutiérrez-Enríquez, Sarah L Kerns, Ramón Lobato-Busto, Alan McWilliam, Barbara Noris Chiorda, Tiziana Rancati, Barry S Rosenstein, Petra Seibold, Elena Sperk, Ana Vega, Liv Veldeman, Tim H Ward, Catharine M West, Paul Symonds, Christopher J Talbot

Published in

Clinical cancer research : an official journal of the American Association for Cancer Research. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

We showed previously that breast cancer patients with certain circadian rhythm genotypes have higher incidences of toxicity when treated with radiotherapy at different times of day. This opens the way to genetically-guided chronomodulation as a cost-effective way to reduce side-effects while preserving treatment efficacy. We aimed to test whether similar time-of-day effects are observed in prostate cancer.
The analysis used the multinational, prospective observational REQUITE prostate cancer cohort (n=1760). All patients received external beam radiotherapy and were followed for two years. Regression analyses were performed in patients with complete data including genotypes and radiotherapy fraction times (n=877). LASSO and logistic regression models incorporated genotypes of SNPs in circadian rhythm genes, time of radiotherapy and their interaction. Primary endpoints were late rectal bleeding and urinary incontinence.
Multivariable models show a significant effect of genotype, time of treatment and an interaction between PER3 genotypes and time for both primary endpoints. The 44% of patients with rs696305 C/C genotype are predicted to reduce their risk of rectal bleeding from 11% when treated at 09:00 to 5% at 17:00. Similarly, the analysis predicts a significant reduction in risk of urinary incontinence from 15% to 5% by avoiding treatment in the middle of the day for patients heterozygous for rs172933 (36% of patients).
These results agree with the earlier findings in breast cancer radiotherapy patients. Interaction between genotype and time of treatment suggests groups of patients could reduce side-effects and improve quality-of-life through chronomodulation.

PMID:
42440347
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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