Scientists and clinicians from the University of Leicester and University Hospitals of Leicester NHS Trust have identified three genes linked to circadian rhythms – our internal body clocks – that are associated with increased risk of side-effects following radiotherapy at particular times in the day.

The results of their study, published online in the journal eBioMedicine, provide more evidence for a personalised approach to radiotherapy, by testing patients for the presence of these three gene variants and then treating at the optimal time.

At least 35,000 women a year in the UK receive radiotherapy as part of treatment for breast cancer. Advances in treatment have doubled survival from this disease in the last 40 years, but a substantial proportion suffer lifelong late effects which can affect quality of life. Breast shrinkage (atrophy) results in changes to the size and appearance of the breast and may cause discomfort.

As part of the EU-funded REQUITE project, the researchers analysed clinical and genotype data from 1690 breast cancer patients across Europe for links with painful inflamed skin (erythema) and breast atrophy, both side-effects of radiotherapy.

Breast shrinkage (atrophy) was seen in 35% of patients and was dependent on body mass index (BMI), radiation dose and the extent of pre-radiotherapy surgery received. Time of treatment was seen to have only a small effect until it was considered in combination with variants in three circadian genes (PER3, CLOCK and RASD1) which then radically altered the probability of developing atrophy. 

This multi-centre observational study is one of the largest studies of its kind collecting blood samples and standardised data longitudinally from 4,400 cancer patients, including yearly follow-up data on side-effects following radiotherapy. Several hospitals in seven European countries (Belgium, France, Germany, Italy, The Netherlands, Spain, UK) and in the US participate in this study. Patients were enrolled until 2017 and followed up in the first two to three years after radiotherapy. In Germany, hospitals in Mannheim, Karlsruhe, Freiburg, Darmstadt, Speyer, Ludwigshafen and Baden-Baden were involved.

Source : REQUITE project