A recent study from the University of Manchester has uncovered genetic variants that may explain why some prostate cancer patients experience increased sensitivity to radiation in specific areas of the rectum. This discovery holds the potential to significantly reduce the risk of severe bowel complications associated with radiotherapy, a condition known as rectal toxicity. The findings, funded by Prostate Cancer UK, were published in the journal Clinical Cancer Research on October 13, 2025.
The research was spearheaded by PhD researcher Artemis Bouzaki, who is also affiliated with The Christie NHS Foundation Trust. Bouzaki’s work represents a pioneering effort to merge genetic data with detailed spatial maps that illustrate how radiation is applied in the rectum. Previous research had already identified the lower posterior region of the rectum as being crucial in terms of rectal toxicities following prostate cancer radiotherapy. However, this study is the first to integrate genetic information into this framework.
“Rectal toxicity is a significant concern for patients receiving radiotherapy for prostate cancer, which is the most common cancer in men and now the most prevalent cancer in England,” Bouzaki stated. “While dose guidelines aim to limit the overall rate of rectal toxicity to around 10%, bowel function often deteriorates during and after treatment. Some patients face severe and persistent complications, such as incontinence or rectal bleeding, which can severely impact their quality of life.”
The research team analyzed data from 1,293 prostate cancer patients who participated in the international REQUITE study, which gathered radiotherapy outcomes from 17 hospitals across Europe and the USA between 2014 and 2016. They categorized patients based on the presence of three genetic variants associated with heightened radiation sensitivity. By employing dose maps of the rectum, developed through earlier methodologies, the study consistently pinpointed risk regions within the lower posterior rectum.
To enhance their analysis, the scientists utilized a specialized approach called Voxel Based Analysis, which examines three-dimensional image data in tiny volume units known as voxels. This technique allows for a more precise identification of smaller areas within organs, correlating higher radiation doses to specific treatment-related side effects.
Co-author and study supervisor, Dr. Alan McWilliam, remarked, “Our work has revealed that patients with certain genetic variants may benefit from lower radiation doses in those specific parts of the rectum. This could significantly enhance their recovery process.” He cautioned that while the findings are promising, further clinical studies will be necessary to validate their safety and efficacy before any modifications to standard treatment protocols are implemented.
The sensitivity of the lower rectum may be attributed to anatomical and functional differences within the rectum itself. These disparities can influence how the area responds to radiation, potentially affected by various genetic variants, including those analyzed in this study.
Dr. Hayley Luxton, Head of Research Impact and Engagement at Prostate Cancer UK, commented, “No two men’s prostate cancers are identical, and treatment choices will vary among individuals. Radiotherapy is a highly effective treatment for prostate cancer, but it can result in life-altering side effects.”
Luxton explained that there are two primary methods to mitigate the side effects caused by radiotherapy: by adjusting the dosage based on genetic factors or by reducing the radiation dose to certain areas of the body. “For the first time, thanks to funding from Prostate Cancer UK and Movember, the Manchester team has combined both approaches. This allows for the fine-tuning of radiotherapy delivery based on a patient’s genetic profile. Personalizing treatment in such a manner aligns with our goal for the future of prostate cancer care. This study moves us closer to ensuring that the right men receive the right treatment at the right time.”
The implications of this research could transform the landscape of prostate cancer treatment, paving the way for more tailored and effective therapies that enhance patient outcomes while reducing the risk of debilitating side effects.
