Closing date: 03/02/2023
MB-PhD Project: Diabetes and pancreatic cancer: prevention and Risk stratification through Mendelian randomisation (DiaRMid)
Initial Intercalation Deadline: 12 December 2022
Interviews: Tuesday 7 March 2023
Final Deadline for Permission to Intercalate (UoM Programmes): 26 May 2023
MB-PhD Start Date: September 2023
Project Keywords: Diabetes, casual interference, pancreatic cancer early detection
Research Opportunity: Intercalated PhD, leading to the award of PhD and MBChB
Applications for this project are now open. Candidates must contact prospective supervisor/s ahead of submitting an application. See the MB-PhD programme page for details of how to apply.
Type 2 diabetes (T2D) occurs in 10% of the population and is a risk factor for pancreatic cancer (PC). Patients with T2D are regularly monitored but there are untapped opportunities to identify high-risk groups for the development of PC, and in turn, implement prevention and risk stratification for the early detection of PC.
Obesity, commonly approximated by excess body mass index (BMI), is a risk factor for T2D and PC. In turn, the causal pathway from T2D to PC might be through hyperglycaemia (approximated by glycated haemoglobin, HbA1c, levels) or hyperinsulinaemia. The study of these inter-relationships using observational epidemiology is fraught with biases. Here, we propose the use of Mendelian Randomisation to investigate the casual effects of T2D liability, HbA1c and insulin levels on the outcome of PC incidence.
Using mainly the UK Biobank (500,000 participants), we will select variants for T2D liability, and HbA1c and insulin levels as genetic instruments to estimate associations with PC. Secondary analyses will test for differences in associations in individuals with and without T2D, and adjustments for BMI.
This thesis will combine expertise in obesity-cancer research (Renehan, Sperrin); pancreatic cancer (Valle); MR (Martin, Gunter) to develop four workstreams (WSs):
WS1: Write a comprehensive UK Biobank application
WS2: Selection of genetic variants as instruments
WS3: Estimate genetic associations with PC
WS4: Secondary analyses to explore for potential pleiotropic effects.
The end product will be a combined clinical and genetic risk stratification tool that will (i) allow testing PC prevention strategies in T2D (e.g. glycaemic control) and (ii) facilitate targeting high-risk T2D individuals for PC screening.
The student will be MCRC-based (integrated into BRC PED theme), link with the HPB research theme, with opportunities for placements to the University of Bristol and IARC, Lyon. The thesis will be minimally impacted if there were recurring COVID restrictions.
About the Renehan Lab
“Since 2014, I have been clinical lead and co-chair for the MCRC Fellowship Training scheme. I have a track record in identifying and nurturing clinical students to achieve high-quality cancer science. I am a co-investigator on the awarded Cancer Research UK Clinical Academic Training Award application and was one of the presenting team to CRUK in March 2019”.
“Lead supervisor meetings are weekly in the first 6 months; fortnightly thereafter. There are monthly lab meetings and monthly virtual journal clubs. Students will present their work and bring new ideas to lab meetings. All PhD studentships include multi-disciplinary inputs with quarterly face-to-face supervisor meetings. As the student matures, they are encouraged to develop autonomy and independence”.
“My group already includes one MB-PhD student who has been ambassadorial with dissemination of information about the MB PhD scheme during the Covid pandemic and who has successfully passed her year 1 viva. The ‘lab’ culture is one of integration, continuity, synergism, cross-covering, and collaboration”.
Publications and Existing Literature
“The Renehan research group regularly publish within the Lancet family of journals and other high-impact journals, often within the framework of large collaborative teams of researchers. The student will undertake a comprehensive literature review in the first months to meet eProg deadlines. The use of systematic review methods and comprehensive cross-tabulations will be encouraged. The student will maintain excellence of knowledge in their field and will be allocated to review subject-specific new publications through the virtual journal club. The student will learn structures and reporting methods for scientific papers using recognised frameworks such as CONSORT and STROBE (Renehan is a member of the STROBE group). The student will be expected to lead on paper(s) arising from their thesis. Authorship contributions will follow recommendations of the ICMJE”.
“The UoM clinical academics on the supervisory team pledge to mentor a successful candidate beyond the MB PhD period into their early academic career. To this end, the student will be educated in academic pathways after PhD including ACF, and ACL posts. The student will be introduced to other aspirating clinical academics and will attend relevant workshops, for example, the Academy of Medical Science. As part of the students training, he/she will attend and present at national and international conferences in cancer (e.g. NCRI conference) and in obesity-relevant fields. The student will be aspirational and will be encouraged to develop autonomy and independence including writing grants for young investigators projects/ award”.
“The #TeamRenehan ethos is very much around including fun within research and enjoying the experience of working closely, often for intense periods, with a diversity of other students and researchers within the group”.
Find out more about the MB-PhD Programme in Manchester and our current MB-PhD students.