RADIOGENFF · RADIOGENOMICS: Finding Genetic Functional Variants Through Fine Mapping
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-04-01 → 2018-03-31
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
RADIOGENOMICS: Finding Genetic Functional Variants Through Fine Mapping
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
Data: CORDIS, © European Union
Project objective
“Radiogenomics” is the study of the genetics of toxicity following radiotherapy. Unintended damage to normal tissues can severely affect up to 5% of patients for years after completion of curative cancer radiotherapy. To date three Genome Wide Association Studies on radiation toxicity in prostate cancer patients have been performed. These studies have identified genetic loci associated with development of radiation-induced toxicity phenotypes in local tissues. To increase the very limited power of each independent study, the three groups are collaborating on a meta-analysis of harmonised toxicity phenotypes (nocturia, urinary frequency, decreased stream and proctitis) and have identified several promising new loci. The proposed activity at the Centre for Cancer Genetic Epidemiology will be fine-scale mapping of these loci identified with the aim of identifying the genetic variants directly responsible for these toxicity phenotypes. The objectives of the proposed research are: 1. For the Researcher to learn advanced genetic epidemiological and fine-mapping skills by participating in team-based analysis of incoming massive, “OncoArray” datasets – which will be analysed at the host institution; 2. Identify and validate additional novel genetic radiation toxicity loci through analysis of specific radiotoxicity SNP-sets on the “Oncoarray” and through additional GWAS meta-analysis; 3. Apply high-level skills, gained in objective 1, to the fine scale mapping of radiation toxicity loci with the aim of to identifying the top genetic causal candidate variants for radiation toxicity; 4. Carry out bioinformatic functional analysis of the top causal candidates to both narrow the candidate list further, and gain understanding of the molecular patho-physiology and genetic mechanisms that mediate the development of radiation-induced toxicity. Knowledge of these will constitute a further step in identifying genetically at-risk groups likely to benefit from personalized radiotherapy.
Original text from CORDIS.
Participants
- THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGECoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union