Many cancer patients receive radiotherapy as part of their treatment, but a minority develop a bad reaction to the radiation. These effects can be acute or long-term, and can range from disfiguring or painful to potentially fatal. There is evidence that genetics partly underlies which patients will tolerate radiotherapy well and which will suffer toxic reactions. We have previously found several genes that protect or predispose to radiation-induced fibrosis, telangiectasia and other affects. This is part of an effort to develop a genetic test which can be used clinically to provide individualised treatment. For example those patients likely to suffer reactions could be offered alternative treatment such as mastectomy, and importantly the resistant patients could be given higher doses of radiation, improving their survival prospects.
We have a project funded by the European Union, called the REQUITE project (www.requite.eu), to collect a cohort of up to 5300 samples from breast, prostate and lung cancer patients and to use this to find risk predictors including genes. We are doing this partly by SNP genotyping and partly through cell-based experiments. Further work is investigating the basic mechanisms of cellular response to radiation.
The project can be experimental, bio-informatics or a mixture of both. Experiment projects may involve assays of DNA damage and repair or cell-based assays for radiation response. Bio-informatics would involve analysing the intersection of genetic, laboratory and clinical data. Some relevant experience needed.
For informal enquiries email Dr Chris Talbot [email protected]
We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.
Talbot CJ, Tanteles GA, Barnett GC, Burnet NG, Chang-Claude J, Coles CE, Davidson S, Dunning AM, Mills J, Murray RJ, Popanda O, Seibold P, West CM, Yarnold JR, Symonds RP. A replicated association between polymorphisms near TNFα and risk for adverse reactions to radiotherapy. Br J Cancer. 2012 Aug 7;107(4):748-53.
Barnett GC, Thompson D, Fachal L, Kerns S, Talbot C, Elliott RM, Dorling L, Coles CE, Dearnaley DP, Rosenstein BS, Vega A, Symonds P, Yarnold J, Baynes C, Michailidou K, Dennis J, Tyrer JP, Wilkinson JS, Gómez-Caamaño A, Tanteles GA, Platte R, Mayes R, Conroy D, Maranian M, Luccarini C, Gulliford SL, Sydes MR, Hall E, Haviland J, Misra V, Titley J, Bentzen SM, Pharoah PD, Burnet NG, Dunning AM, West CM. A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity. Radiother Oncol. 2014 May;111(2):178-85.
Tanteles GA, Murray RJ, Mills J, Barwell J, Chakraborti P, Chan S, Cheung KL, Ennis D, Khurshid N, Lambert K, Machhar R, Meisuria M, Osman A, Peat I, Sahota H, Woodings P, Talbot CJ, Symonds RP. Variation in telangiectasia predisposing genes is associated with overall radiation toxicity. Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):1031-6.