Circadian genotypes in PER3 and time of prostate cancer radiotherapy interact to affect risk of late side effects in the prospective REQUITE cohort

A study of patients with breast cancer showed that those with certain circadian rhytm genotypes have higher incidences of toxicity when treated with radiotherapy at different times of day. Analysis of the multinational, prospective observational REQUITE prostate cancer cohort (n=1760) investigated whether similar time-of-day effects are observed in prostate cancer. All patients received external beam radiotherapy and were followed for 2 years. Regression analyses were performed in patients with complete data, including genotypes and radiotherapy fraction times (n=877). Primary endpoints were late rectal bleeding (RB) and urinary incontinence (UI). Multivariable models show significant effects of genotype, treatment timing, and the interaction between PER3 genotypes and treatment timing for both primary endpoints. The 44% of patients with the rs696305 C/C genotype are predicted to reduce their risk of RB from 11% when treated at 9:00 am to 5% when treated at 5:00 pm. Similarly, the analysis predicts a significant reduction in the risk of UI from 15% to 5% by avoiding treatment in the middle of the day for patients heterozygous for rs172933 (36% of patients). The authors conclude that these results suggest that groups of patients could reduce side effects through chronomodulation.