2026-04-17T04:28:55Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/83612024-12-13T10:01:05Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Webb, Adam J. author Harper, Emily author Rattay, Tim author Aguado-Barrera, Miguel E. author Bourgier, Celine author Gutierrez Enriquez, Sara author Seoane Ramallo, Alejandro author Reyes López, Victoria author Azria, David author 2022-10-27T09:03:55Z 2022-10-27T09:03:55Z 2022-10 Breast cancer; Circadian rhythm; Radiotherapy Cáncer de mama; Ritmo circadiano; Radioterapia Càncer de mama; Ritme circadià; Radioteràpia Background Circadian rhythm impacts broad biological processes, including response to cancer treatment. Evidence conflicts on whether treatment time affects risk of radiotherapy side-effects, likely because of differing time analyses and target tissues. We previously showed interactive effects of time and genotypes of circadian genes on late toxicity after breast radiotherapy and aimed to validate those results in a multi-centre cohort. Methods Clinical and genotype data from 1690 REQUITE breast cancer patients were used with erythema (acute; n=340) and breast atrophy (two years post-radiotherapy; n=514) as primary endpoints. Local datetimes per fraction were converted into solar times as predictors. Genetic chronotype markers were included in logistic regressions to identify primary endpoint predictors. Findings Significant predictors for erythema included BMI, radiation dose and PER3 genotype (OR 1.27(95%CI 1.03-1.56); P < 0.03). Effect of treatment time effect on acute toxicity was inconclusive, with no interaction between time and genotype. For late toxicity (breast atrophy), predictors included BMI, radiation dose, surgery type, treatment time and SNPs in CLOCK (OR 0.62 (95%CI 0.4-0.9); P < 0.01), PER3 (OR 0.65 (95%CI 0.44-0.97); P < 0.04) and RASD1 (OR 0.56 (95%CI 0.35-0.89); P < 0.02). There was a statistically significant interaction between time and genotypes of circadian rhythm genes (CLOCK OR 1.13 (95%CI 1.03-1.23), P < 0.01; PER3 OR 1.1 (95%CI 1.01-1.2), P < 0.04; RASD1 OR 1.15 (95%CI 1.04-1.28), P < 0.008), with peak time for toxicity determined by genotype. Interpretation Late atrophy can be mitigated by selecting optimal treatment time according to circadian genotypes (e.g. treat PER3 rs2087947C/C genotypes in mornings; T/T in afternoons). We predict triple-homozygous patients (14%) reduce chance of atrophy from 70% to 33% by treating in mornings as opposed to mid-afternoon. Future clinical trials could stratify patients treated at optimal times compared to those scheduled normally. EU-FP7. http://hdl.handle.net/11351/8361 Mama - Càncer - Radioteràpia Radioteràpia - Complicacions Ritmes circadiaris PHENOMENA AND PROCESSES::Physical Phenomena::Radiation::Radiation Exposure::Radiation Injuries DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms Other subheadings::Other subheadings::Other subheadings::/radiotherapy DISEASES::Pathological Conditions, Signs and Symptoms::Pathological Conditions, Anatomical::Atrophy FENÓMENOS Y PROCESOS::fenómenos físicos::radiación::exposición a la radiación::lesiones por radiación ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama Otros calificadores::Otros calificadores::Otros calificadores::/radioterapia ENFERMEDADES::afecciones patológicas, signos y síntomas::afecciones patológicas anatómicas::atrofia Treatment time and circadian genotype interact to influence radiotherapy side-effects. A prospective European validation study using the REQUITE cohort