In the European Union in 2003 approximately 17.8 million people have had a past diagnosis of cancer. Improvement in diagnosis and treatment leads to increased life-expectancy. Thus, the number of cancer survivors is expected to rise. As cancer increasingly becomes a chronic disease, patients’ quality-of-life (QoL) needs to be addressed. Half of all cancer patients (and ~60% of those treated with curative-intention) receive radiotherapy at some point. Radiotherapy schedules have been developed to maximize tumour-kill while minimizing surrounding normal tissue toxicity. However, approximately 5% of radiotherapy-treated patients suffer from severe long-term side-effects and yet more experience moderate toxicity, such as incontinence or chronic pain, which can have a marked effect on QoL. The identification of radio-sensitive patients would permit better-tailored radiation doses; thus, toxicity could be minimised in radiation-sensitive patients and, contrastingly, radiation-tolerant patients could be given increased tumour-doses, raising their probability of local recurrence-free survival.
The objectives of the proposed research, structured by working packages (WP), are:
WP1. For the Researcher to learn advanced genetic epidemiological and fine-mapping skills by participating in team-based analysis of large cohorts of genotyping data
WP2. Identify and validate additional novel genetic radiation toxicity genomic regions through analysis of specific radiotoxicity genetic variants
WP3. Apply high-level skills, gained in objective 1, to the fine scale mapping of radiation toxicity genomic regions with the aim of identifying the most likely causal variants for radiation toxicity
WP4. Carry out bioinformatic functional analysis of the top candidate variants to both narrow the candidate list further, and gain understanding of the molecular and genetic mechanisms that mediate the development of radiation-induced toxicity
