Key gene variations predict patients’ risk for radiotherapy side effects

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15 Jul 2014

Key genetic variants may affect how cancer patients respond to radiation treatments, according to a study, involving researchers at The University of Manchester, published recently in the journal Nature Genetics.

The research team, which saw scientists from The University of Manchester – part of the Manchester Cancer Research Centre - work with researchers in Santiago de Compostela, Spain, University of Cambridge and Mount Sinai New York, found that variations in the TANC1 gene were associated with a greater risk of side effects after radiotherapy for prostate cancer. 

The current results are based on a genome-wide association study, a type of study where researchers examine numerous genetic variants to see if any of them are associated with side effects, which can appear years after treatment was completed.

For the study, the Manchester team collected blood samples from over 600 patients who had radiotherapy for prostate cancer. The blood samples were collected from patients across the UK as part of the Cancer Research UK funded RAPPER study. Patients were screened for over two million genetic markers, and  monitored for at least two years to assess side effects from the radiation. Nearly 1,500 patients were studied in total to find out which genetic markers were consistently associated with the development of side effects following radiotherapy.

The work is a major milestone for research trying to identify the genetic variants that increase a cancer patient's risk of side effects after radiotherapy. Many thousands of patients will need to be studied to find enough genetic variants to have a genetic test that can be used to help cancer patients. When enough variants are found then a test could be used to personalise radiotherapy to reduce the number of cancer survivors with long-term side effects after treatment. 

Catharine West, Professor in Radiation Biology at The University of Manchester, led the setting up of an international Radiogenomics Consortium in Manchester in 2009 to encourage scientists to collaborate to do this sort of research. Professor West said: "A consortium approach is essential so that enough patients are studied. The Nature Genetics paper is the result of that first meeting in Manchester. We now need to study perhaps 50,000 patients to identify enough genetic variants for a test that can be used clinically. Another 5,000 samples are being analysed this year and we are collecting more samples in other studies. So the paper is an exciting first step but there is a lot more work that needs to be done."

This study was conducted in partnership with USC University Hospital Complex and Fundación Pública Galega de Medicina Xenómica-SERGAS, Santiago de Compostela, Spain; University of Cambridge and The Christie NHS Foundation Trust. Cancer Research UK funded the UK RAPPER study. 
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