A research team led by the Twin Research Department at King’s with colleagues from Imperial College London, The Wellcome Trust Sanger Institute, Brisbane Institute of Medical Research and Leeds has found new genes for melanoma in one of several studies published in Nature Genetics this week.
Melanoma incidence has risen rapidly over the last 30 years so discovering genes which may predict those most at risk of this deadly tumour may prevent increased cases of mortality. It is already known that large numbers of moles (nevi) are the most important risk factor for melanoma (more so than over exposure to sunshine or use of sunbeds).
Professor Tim Spector, Senior author and Director of the Department of Twin Research added. ‘These novel genes regulating moles can lead to a doubling in melanoma risk. The study shows the unique value of the TwinsUK volunteer cohort. Twins have helped us over the last 13 years to find that moles are heritable and then isolating the gene regions and now the actual genes involved.’
The King’s team had previously shown that genes influencing the number of moles (nevi) might overlap with those for melanoma. The recent Genome-Wide Association (GWA) study allowed scientists to examine differences in people’s DNA code at a third of a million sites and through this also uncovered two novel genes for melanoma.
For this project researchers performed a Genome Wide Association study looking at common changes in genes for nevus counts in 1,524 healthy adult female twins from the TwinsUK registry using 300,000 genetic markers known as (SNPs). SNPs in two genes, on chromosome 9 (MTAP) and chromosome 22 (PLA2G6), were significantly associated with higher mole (nevus) counts.
Dr Veronique Bataille, Consultant Dermatologist in charge of the skin research programme at the Twin Research Department at King’s, and first co-author of the study said: ‘These new genes may be useful for screening but will also help in understanding melanoma genetic pathways with possible therapeutic targets.’
These initial results were replicated in an independent sample of 4,107 adolescent twins from Brisbane. These two genes also predict melanoma risk in several thousand cases of melanoma from around the world (the Genomel Melanoma Consortium). The risk of having double copies of both these gene variants increases melanoma risk by up to two fold. The effect appears to be mediated by the increased number of moles (nevi).
Dr Bataille went on to say: ‘Moles are common in all European populations and the chance of any of them changing into a melanoma is very small. However, if you do have many moles, especially large moles, it is recommended that you have them checked.’
Notes to editors
The paper Loci at 9p21 and 22q13 harbour alleles for development of cutaneous nevi and melanoma has been published online in Nature Genetics. To view the paper, please visit: http://www.nature.com/ng/index.html
Professor Tim D Spector is the senior author – Department of Twin Research and Genetic Epidemiology, King’s College London, UK.
Tel: +44 (0) 20 7188 6765, Email: firstname.lastname@example.org
Dr Mario Falchi PhD is the first author and currently works at the department of Genomic Medicine, Imperial College London
Dr Veronique Bataille – Joint first author and Principal Dermatologist on study and melanoma expert.
Tel: +44 (0)20 7188 6765, Email: email@example.com
The Department of Twin Research and Genetic Epidemiology at King’s College London has a database of 11,000 twins and studies a wide variety of diseases and human behavious and traits, leading to several high profile publications. For more information and pdf-copies of other publications please phone: +44 (0)20 7188 6765 or visit the website: www.twinsUK.ac.uk
The research was funded by the Wellcome Trust and the NHS NIHR. Genotyping was performed by the Sanger Institute.
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