The molecular epidemiology of prostate cancer: Assessing the association between genome-wide DNA methylation and risk for aggressive prostate cancer - CRUK DPHIL SCHOLARSHIPS AVAILABLE
DNA methylation is involved in maintaining genomic integrity and regulating gene expression, and may be a reversible biological process. Elucidating the associations of DNA methylation with prostate cancer risk has the potential to guide strategies for prevention, although few studies have examined this in relation to prostate cancer and no studies have been large enough to study aggressive disease.
Peripheral blood DNA methylation is of particular interest as a biomarker of exposure to a wide range of endogenous (e.g. inflammation, hormones) and exogenous factors (e.g. smoking, BMI, alcohol), and may provide insights into epigenetic mediators of cancer risk factors. Recent methodological developments allow the appraisal of the causal contribution of DNA methylation as a mediating mechanism using Mendelian randomisation.
The DPhil Project: This is a project on the molecular epidemiology of prostate cancer risk in the European EPIC study.
The exact project will be shaped by the student with the supervisors, but one area of possible research is into the epidemiology of epigenomic measures and prostate cancer. As well as prospective analyses of disease risk, the research may also examine the interrelationships of DNA methylation with other biomarkers and risk factors, including hormonal and nutritional factors, physical activity and adiposity.
The EPIC cohort includes ~150,000 men recruited in 1993-2000 in eight countries in Europe, with extensive genetic and phenotypic data, including biochemical assays from blood samples, and over 3 million person years of follow-up (https://www.ceu.ox.ac.uk/research/epic-prostate). More than 7000 men have been diagnosed with incident prostate cancer, of whom 2000 had aggressive disease. Nested case-control analyses to date in EPIC have included 1000 to 3500 prostate cancer cases. Students may also analyse data from the UK Biobank cohort, in which 5700 incident prostate cancers have been diagnosed to date.
The project will involve the analysis of molecular, biomarker and questionnaire data, and the incorporation of genetic data in epidemiological analyses. The student may also conduct Mendelian randomisation analyses of risk factors in relation to risk for aggressive prostate cancer, using data from the PRACTICAL consortium with information on 200,000 men and more than 6000 cases of aggressive prostate cancer.
RESEARCH EXPERIENCE, RESEARCH METHODS AND TRAINING
This project will provide the successful applicant with excellent training in large-scale molecular epidemiology and the statistical analysis of prospective data. It will provide opportunities to network with other investigators both locally and with international collaborators. The student will receive training in conducting literature reviews and writing academic papers for peer-reviewed journals and will work closely with a strong interdisciplinary team of researchers with expertise in epidemiology, molecular epidemiology, epigenetics, statistics, clinical medicine and biochemistry.
FIELD WORK, SECONDMENTS, INDUSTRY PLACEMENTS AND TRAINING
The student will be co-supervised by Prof Caroline Relton, an experienced epigeneticist at the University of Bristol. It is anticipated that the student will attend epigenetics and Mendelian randomisation training, as well as making research visits to the Bristol team and our EPIC collaborators at the WHO International Agency for Research on Cancer (IARC), Lyon, France who are working on similar projects.
This project will suit someone with an interest in molecular epidemiology and the aetiology of cancer, who is looking to expand their skills and experience of epidemiological study design and the statistical analysis of molecular, biomarker and other epidemiological data, as well as Mendelian randomisation analyses.