The Genetic Epidemiology of Susceptibility to Melanoma and Relapse from Melanoma
The melanoma group has worked on the genetic and environmental susceptibility to melanoma since 1995. The core project has been directed towards understanding and identifying melanoma susceptibility genes in families, which is funded by Cancer Research UK (fig 2). The project is also funded by the NIH to take a candidate gene approach to finding new susceptibility genes. In December 2005, JNB, as chairman of the melanoma genetics consortium, GenoMEL, became Coordinator of an EU funded NoE. The NoE runs from 2005-2010 and funds data collection from melanoma families in multiple centres in Europe, North America and Australia. The grant also funds a genome wide search for new low to medium penetrance susceptibility genes, and psycho-oncology projects. The Leeds melanoma group has been busy continuing effective management of this 10.4 million euro project.
The second core programme is directed towards understanding relapse from melanoma. A number of long-term studies have been set up to allow the group to address these issues. A study of late relapsing melanoma patients has now closed. The most interesting finding has been the demonstration of a protective effect of vitamin D supplementation on relapse. which is currently being evaluated in an NCRN funded national study. In all of these studies, epidemiological data are collected by questionnaire from the patients, serum is stored and as is DNA to allow investigation of the germline. Consent is also obtained from the patients to allow access to their paraffin embedded tumours so that we may study gene expression in these blocks using the Illumina DASL platform.
Figure 1.
Figure 2. Mutations of the CDKN2A locus with families at risk of melanoma.
Harland, M., C. F. Taylor, P. A. Chambers, K. Kukalizch, J. A. Randerson-Moor, N. A. Gruis, F. A. de Snoo, J. A. Ter Huurne, A. M. Goldstein, M. A. Tucker, D. T. Bishop and J. A. Bishop (2005). “A mutation hotspot at the p14ARF splice site.” Oncogene 24: 4604-4608.
Goldstein AM, Chan M, Harland M, et al. Features associated with germline CDKN2A mutations: A GenoMEL study of melanoma-prone families from three continents. J Med Genet 2006.
Downing A, Newton-Bishop JA, Forman D. Recent trends in cutaneous malignant melanoma in the Yorkshire region of England; incidence, mortality and survival in relation to stage of disease, 1993-2003. Br J Cancer 2006;95(1):91-5.