Group Leader: Professor Julia Newton-Bishop
We seek to improve melanoma prevention by identifying which individuals are most susceptible to the disease, and what lifestyle factors are causal for melanoma within the susceptible. We use genetic epidemiology to do this: using data on inherited genes and data collected from the patient and his/her clinical notes using questionnaires.
We also carry out research to identify what factors, such as genetics and lifestyle, predict survival after melanoma. The ultimate aims of this work are to:
- Find tests which patients and their medical teams can use to give a prognosis and predict which treatments would be most effective for advanced melanoma (personalised medicine).
- Identify lifestyle factors which might improve survival (such as 'healthy' lifestyles, vitamin D, or coincidental exposure to common drugs such as metformin or aspirin) or might harm it.
- Better understand the science of interactions between the patient and the tumour. If we can do this then we will be able to inform new drug development.
Work on susceptibility
The patterns of sun exposure associated with melanoma risk have been studied and a complex relationship demonstrated. Sunny holidays and sunburn are robust risk factors for melanoma but regular, moderate sun exposure was shown to be protective in our data and we are exploring the biological explanation for this apparent discrepancy.
Genome-wide association studies
Genome-wide association studies are those in which blood tests are performed on melanoma patients and people without melanoma. The nucleic information (DNA) in the white cells of the blood is then examined across the genome and variations considered. A variant is a section of DNA which differs between people. Many variants have no medical significance but some indicate biological differences between people which relate to susceptibility. We have mapped 16 low-medium penetrance susceptibility loci associated with melanoma risk. Many of these genetic variants associated with risk are in genes that have a role in controlling cell division and DNA repair, telomere function or in determining pigmentation. However, some of the variants are in genes that have no established role in melanoma. It is likely that understanding their role will tell us something important about melanomagenesis. We are working with UK Biobank data to test the degree to which these variants predict risk in the UK population.
Whole exomic sequencing
In collaboration with Dr David Adams at the Wellcome Trust Sanger Institute we are investigating familial melanoma samples. Sequencing provides more detailed genetic data on coding DNA and we are using this technique within the GenoMEL consortium to find new high-risk genes. This work will help genetic counsellors advising families prone to melanoma and will increase our understanding of the biological events which increase melanoma risk very significantly. We have recently reported the identification of newly discovered familial melanoma genes, including in Nature Genetics.
Work on survival
Cohorts of melanoma patients
Funded by the NIH and Cancer Research UK, we have built patient cohorts to study lifestyle factors having an effect on survival. We have published evidence that low vitamin D levels are associated with poorer prognosis.
Somatic profiling means using new technologies (often referred to as omics) to describe the genetic changes in tumours. Using next generation sequencing and gene expression studies we are describing important somatic profiles of melanoma. This work is designed to inform knowledge of melanoma biology and as biomarker discovery.
Exposures influencing prognosis
We are exploring evidence that incidental drug exposures, such as NSAIDs or immunosuppressants, may moderate survival expectation for melanoma patients using the Leeds Melanoma Cohort and the ResearchOne general practice database.
Our work is greatly advanced through international collaboration. We have fostered three major melanoma research consortia, GenoMEL, BioGenoMEL and MELGEN, addressing different areas of research. GenoMEL has led the way in understanding familial melanoma, and fostered the development of BioGenoMEL in order to understand the determinants of melanoma survival. MELGEN is creating a co-operative European environment for melanoma research and training, with the ultimate aim of improving precision medicine for patients with the disease.
- Professor Julia Newton-Bishop, Group Leader
- Professor Tim Bishop, Epidemiologist
- Katie Cairns, Personal Assistant and Project Manager of the Leeds Testicular Cancer Study
- Ms May Chan, Database Manager
- Dr John Davies, Senior Statistician
- Ms Joanne Gascoyne, Database Manager
- Dr Mark Harland, Senior Scientific Officer
- Dr Jonathan Laye, Senior Histology Technician
- Tracey Mell, Technician
- Dr Jérémie Nsengimana, Senior Statistician
- Dr Juliette Randerson-Moor, Laboratory Manager/MELGEN Manager
- Mr Christy Walker, Senior Research Nurse and Project Coordinator
- PhD students, currently Sathya Muralidhar, Joanna Pozniak, Rohit Thakur, Joey Mark S. Diaz and Adam Trower
We receive support from a wide range of funders including Cancer Research UK, the Medical Research Council (MRC), the Leeds Hospital Charitable Foundation, the US National Institutes of Health (NIH), Melanoma Focus, the Melanoma Research Alliance (MRA) and the EU's Marie Skłodowska-Curie actions.
We are also grateful to all of our research participants and former staff members; both have been crucial to our achievements.