The molecular epidemiology of prostate cancer
The aetiology of prostate cancer is largely unknown. The goal of this DPhil project will be to contribute to the evidence on potentially modifiable risk factors for prostate cancer, through epidemiological studies of biomarkers of risk, and of correlated genetic, dietary, lifestyle and hormonal factors, as well as through genetic analyses such as Mendelian randomisation studies.
In prospective analyses and individual participant meta-analyses we have shown that a high circulating concentration of insulin-like growth factor-I (IGF-I) is associated with prostate cancer risk, and elevated circulating IGF-I remains the only established and potentially modifiable risk factor. Less is known about the role of IGF-II or its main binding proteins. We have also found that protein intake may be positively associated with risk, and diets high in protein can increase circulating IGF-I. The insulin-like growth factor system is related to proliferation, tumour growth and inhibition of apoptosis. A number of common genetic variants with moderate effects on prostate cancer risk have been identified by genome-wide association studies and we conduct studies collaboratively with several large international genetics consortia. Future studies will involve analysing and interpreting genetic, biomarker (hormonal, nutritional and metabolomic), dietary and lifestyle data from EPIC, UK Biobank and other cohorts, with a focus on prostate cancer.
For this DPhil project, the student will review the literature and the data available, and then define a set of hypotheses to investigate through their DPhil research. The project will potentially use data and biological samples from the European Prospective Investigation into Cancer and Nutrition (EPIC), a European cohort of approximately 500,000 individuals, of whom over 7,000 men have incident prostate cancer, and from UK Biobank, a cohort of 500,000 people recruited in 2006-2010 from across Britain. Nested case-control and cohort studies will be undertaken to investigate the association of circulating biomarkers with prostate cancer risk. Data will also be available from UK Biobank and the PRACTICAL consortium, an international genetics consortium, to conduct research on genetic risk factors for cancer and Mendelian randomisation studies.
RESEARCH EXPERIENCE, RESEARCH METHODS AND TRAINING
This project provides an opportunity to use a range of methods to assess the relationship between molecular factors (hormonal, nutritional and metabolic biomarkers and genetic data) and risk for prostate cancer, overall and by tumour subtype.
field work, secondments, industry placements and training
This project will provide the successful applicant with excellent training in large-scale epidemiology, the statistical analysis of prospective data (cohort and nested-case-control) and will provide opportunities to network with other investigators both internally and with international collaborators. He/she 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, statistics, clinical medicine and biochemistry.
This project will suit someone with an interest in the aetiology of cancer and in molecular epidemiology, who is looking to expand their skills and experience in epidemiological study design and the statistical analysis of biomarker, metabolomics and genetic epidemiological data.