Jobs

The Melville Trust PhD Studentship

Reports to: Project Supervisor

Job Purpose: The trustees invite applications for Melville Trust PhD Studentships. These awards provide three years support for promising cancer researchers, with the aim that some will consider a career in research, leading to submission of a PhD thesis.

Please see PDF below for the full studentship description.

The Melville Trust Vacation Scholarship

Reports to: Project Supervisor

Job Purpose: These awards provide promising undergraduates with hands-on experience of cancer research during the Summer vacation, with the aim of encouraging them to consider a career in research.

Scholarships are available for six to eight weeks' work and currently provide a stipend of £300 per week, which will be paid after receipt and approval of the formal short report of the work conducted.

Please see PDF below for the full scholarship description.

Exploring the use of qFIT as part of the assessment of lower GI symptoms: The impact of genetic effects on cancer risk and bleeding tendency.

Proposed Supervisor: Professor MG Dunlop, Academic Coloproctology, Institute of Genetics and Cancer and Edinburgh Colorectal Surgery, Western General Hospital, Edinburgh.

Contact: malcolm.dunlop@ed.ac.uk

Quantitative faecal immunological testing (qFIT) for human haemoglobin in the stool has been rolled out in Scotland as a screening test for population bowel cancer screening. Similarly, it is soon to be rolled out in England as a screening test, albeit at a higher qFIT threshold and older age-group than in Scotland. The test performance metrics have been established for screening the general population, the thresholds of 80ug/g has been applied in Scotland, whilst in England a threshold level of 140ug/G is being mooted.  There is a critical balance between qFIT test sensitivity and specificity, which directly impacts on demand and capacity of downstream clinical investigation – namely colonoscopy.

Led by Professor Dunlop and Miss FVN Din, qFIT is being rolled out (1^st May 2018) for all symptomatic referrals within Lothian - in parallel with colonoscopy (or CT colonography). This will allow gold standard assessment of qFIT test performance at various thresholds. Assessment of qFIT levels will be conducted in 18,000 patients (6000 referrals annually) without influencing clinical decision-making by including information on stool hHb level as assessed by qFIT. This approach has never been carried out in such a large population and so offers unique opportunity for research with implications likely to have direct impact on health outcomes. This fellowship aims to explore the capacity and caseload demand on colonoscopy services by modelling different thresholds, with the ultimate aim of incorporating patient-specific threshold levels dependent on overall prediction of significant pathology. Varying qFIT thresholds will be assessed using risk models developed to include demographics, symptoms, screening history, family history and genetics SNP marker data. This will be the main focus of the planned fellowship. Ethical approvals are already in place to recruit patients attending secondary care for genetic testing linked with all of the above variables. A specific focus of the proposed short term fellowship will be to study the impact of bleeding tendencies in symptomatic people who attend with positive (and negative) qFIT tests at various thresholds. Quantitative assessment of coagulation cascades – in particular von willebrand factor - will be conducted and genomewide genotyping arrays will be run on all recruits to enable genetic prediction of coagulation and bleeding tendencies in the tested population using mendelian randomisation. There are already over 70 common genetic variants shown to impact on vwf levels and this approach will be the first to directly assess the impact of these genetic variants on bleeding in the gut, as measured by qFIT. This is a completely untapped area of research that will be unique to the proposed fellowship, with the aim of generating pilot data and expertise that could lead to successful funding application for a research fellowship to MRC or CRUK.

The Colon Cancer Genetics Groups have excellent laboratory facilities and all the necessary expertise to explore epidemiology and conduct genetic association studies at scale, as well as translate the results to meaningful clinical endpoints. The successful candidate will gain training and exposure to clinical and translational research approaches, genetics, statistics and statistical genetics and will be part of a vibrant research environment in the CCGG which has a broad mix of scientific, clinical academics, technicians and PhD students all research-focused on combating colorectal cancer for early detection and prevention.

Relevant background references

• Van Loon et al. Genome-wide association studies identify genetic loci for low von Willebrand factor levels. Eur J Hum Genet 2016; 24:1035-40.
• Smith NL et al.  Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation 2010; 121:1382-92.
• Quyn et al. Application of NICE guideline NG12 to the initial assessment of patients with lower gastrointestinal symptoms: not FIT for purpose? Ann Clin Biochem 2018;55: 69-76.
• Zheng J et al. Recent Developments in Mendelian Randomization Studies. Curr Epidemiol Rep 2017; 4:330-345.