A groundbreaking study led by University of Manchester scientists has identified genetic variants which make some patients more sensitive to radiation in specific parts of the rectum than others.
The knowledge could reduce the risk of severe bowel complications from radiotherapy, known as rectal toxicity, heralding a more personalised approach to prostate cancer treatment.
The study, funded by Prostate Cancer UK, is published in Clinical Cancer Research today.(13/10/25).
The study was led by PhD researcher Artemis Bouzaki from The University of Manchester, who is also an honorary researcher at The Christie NHS Foundation Trust.
Her approach is the first study to combine genetic data with detailed spatial maps of where radiation is delivered in the rectum.
Though scientists have already identified the lower posterior of the rectum as significant for rectal toxicities after prostate cancer radiotherapy, the study is the first to incorporate genetic information into the framework.
"Rectal toxicity is a significant concern for patients receiving radiotherapy for prostate cancer, the most common cancer in men and now the most common cancer in England," she said.
"Although dose guidelines limit the overall rate of rectal toxicity to around 10%, bowel function nevertheless often deteriorates over the course of treatment and beyond.
"Some patients experience severe, persistent complications, such as incontinence, or rectal bleeding, permanently affecting their quality of life."
The scientists analysed data from 1,293 prostate cancer patients as part of the international REQUITE study, which collected radiotherapy outcomes from 17 hospitals in Europe and the USA between 2014 and 2016.
For each of three genetic variants linked to increased radiation sensitivity, patients were grouped based on whether they carried the variant.
They were analysed alongside dose maps over the surface of the rectum - based on a methodology developed by the team in their earlier work- which showed the risk regions were consistently in the lower posterior rectum.
The scientists used a special way of analysing 3D image data by looking at it in tiny volume units called voxels, the 3D equivalent of a pixel.
Instead of just measuring overall dose averages in a region, Voxel Based Analysis analyses the data voxel by voxel across the entire image. This allows smaller regions of organs to be identified, where more radiation dose is linked to different treatment side-effects.
Co-author and supervisor of the study, Dr Alan McWilliam from the University of Manchester added: "Our work has revealed that patients with certain genetic variants may benefit from lower radiation doses in those specific parts of the rectum, which could make a significant difference to their recovery.
"However, these findings are preliminary, and clinical studies will be necessary to confirm their safety and effectiveness before any changes are made to standard treatment."
One reason why the lower part of the rectum may be particularly sensitive is that the higher and lower parts of rectum have anatomical and functional differences which could influence their response to radiation.
The differences play a key role in inflammation and immune response and are likely to be affected by different genetic variants, including the ones analysed by the researchers.
Dr Hayley Luxton, Head of Research Impact and Engagement at Prostate Cancer UK, said: "No two men's prostate cancers will be the same, and different men will opt for different treatment. We know that radiotherapy is an extremely effective way to treat men with prostate cancer. However, it can have life changing side effects for patients.
"There are two ways to limit the side effects caused by radiotherapy - either through adjusting dosage to account for genetics or by reducing the dose to certain areas of the body.
"For the first time, thanks to Prostate Cancer UK's funding alongside Movember, the team in Manchester have combined both methods, and can now fine-tune the delivery of radiotherapy based on a man's genetics.
"The ability to personalise treatment in this way is exactly the direction we want prostate cancer care to head in. This study helps bring us that much closer to making sure the right men get the right treatment, at the right time."
