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Understanding Aspirin adverse effect: therapeutic implications for a cancer chemopreventive drug


Project Description

Recent findings have shown that aspirin taken for several years at doses of approximately 100 mg daily, similar to dosing used for cardio-prevention, reduces incidence and mortality due to colorectal and other types of cancer. A careful assessment of benefits and harms is required to assess suitability of aspirin as a prophylactic public health measure. However, comprehensive population-level data on harms are lacking. GI complications are increased by about 60% due to low-dose aspirin use but are fatal only in a very small proportion of individuals younger than 70 years of age (Lancet 2009).

The aim of this PhD project is to elucidate specific pathways and genes associated with GI bleeding due to aspirin intake and generate a list of biomarkers specific to adverse effects.
1. Aspirin for Cancer Prevention (AsCaP) Collaboration aspirin’s associated with GI bleeding project
This project consists of producing a metanalysis by connecting with all members of the AsCaP collaboration and aggregate all genomic data available from several trials in order to create one of the biggest studies evaluating genetic and epigenetic predisposition to GI bleeding related to Aspirin.
2. Methylation profiling of whole genome to uncover responsiveness to low-dose aspirin in colorectal cancer cohort from Add-aspirin cohort
Here we will obtain DNA from patients and run several NGS assays (RNA seq, Methylome, SNPs analysis) to identify epigenetic signatures specific to aspirin adverse effects in aspirin trials. In this respect, it would be interesting to gain further insight into the contribution of the modulation of epigenetic mechanisms in the overall mechanisms of action of aspirin related to GI bleeding.
Informal enquiries can be made to Dr Belinda Nedjai:

How to apply
Your application should consist of a CV and contact details of two academic referees. You must also include a personal statement (1,000 words maximum) describing your suitability for the selected project including how your research experience and interests relate to the project.

Please submit your application to: Brenda Bell

Closing date: 27th March 2020
Formal interviews: TBC

Funding Notes

This 3 year PhD studentship is funded by Cancer Research UK and comes with a tax-free stipend of £21,000. It is open to UK Nationals, EEA/Swiss migrant workers and non-UK nationals with indefinite leave to remain in the UK who will have three years ordinary residence in the EU prior to the start of the studentship. University tuition fees (at UK/EU levels) will be met by the funding body.

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