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Moles and melanoma -- researchers find genetic links to skin cancer

New research has shown why people with the greatest number of moles are at increased risk of the most dangerous form of skin cancer.

The study, led by Professors Julia Newton Bishop and Tim Bishop of the Melanoma Genetics Consortium (GenoMEL) at the University of Leeds, looked at more than 10,000 people, comparing those who have been diagnosed with melanoma to those who do not have the disease.

Researchers across Europe and in Australia, looked at 300,000 variations in their research subjects' genetic make-up, to pinpoint which genes were most significant in developing melanoma – a disease which causes the overwhelming majority of skin cancer related deaths. Their findings are published in the journal Nature Genetics.

Across the large sample, a number of clear genetic patterns emerged.

It is already well known that red-haired people, those with fair skin and those who sunburn easily are most at risk of melanoma, and the people who had been diagnosed with melanoma were found to be much more likely to be carrying the genes most closely associated with red hair and freckles. "This is what we expected to find," said Professor Bishop of the Leeds Institute of Molecular Medicine and the Cancer Research UK Centre at Leeds. "But the links seemed to be much stronger than we anticipated."

"We had known for some time that people with many moles are at increased risk of melanoma. In this study we found a clear link between some genes on chromosomes 9 and 22 and increased risk of melanoma. These genes were not associated with skin colour," he added.

"Instead, in joint research with colleagues at King's College London and in Brisbane who counted the number of moles on volunteer twins, we showed that these genes actually influenced the number of moles a person has."

Around 48,000 people worldwide die of melanoma each year. It is more common in males and those with pale skin – and is on the increase. It is widely believed that the increase in melanomas is largely due to social and behavioural activities, such as increased exposure to the sun, partly caused by the availability of cheaper foreign holidays. Sunny holidays increase the risk because it is intermittent sun exposure which causes melanoma rather than daily exposure over longer periods of time.

Even so, the process by which sunlight and genetics combine to cause cancer in some people, is still poorly understood, as Professor Bishop explained: "If you take the people who have the greatest exposure to sunlight – those who work outside for example – and compare them to those with the least exposure, their risks of getting skin cancer are actually quite similar. Statistically, the differences are quite negligible.

"What we do know is that the combination of particular genes and a lifestyle of significant sun exposure is putting people at greatest risk."

The research shows that there are at least five genes which influence the risk of melanoma. A person carrying all the variants associated with an increased risk is around eight times more likely to develop melanoma than those carrying none, though the majority of people carry at least one of these variants.

Sara Hiom, Cancer Research UK's director of health information, said: "The more we can understand malignant melanoma through research like this the closer we should get to controlling what is an often fatal cancer. This study confirms Cancer Research UK's advice in its SunSmart campaign that people with lots of moles – as well as those with red hair and fair skin – are more at risk of the most dangerous form of skin cancer and should take extra care in the sun.

"The research goes further and identifies the actual genes associated with this increased risk."

For advice on moles, please see the Patient Information Section at Moles are normal, but people should seek the advice of their doctor if a mole changes in shape, size or colour or for anything new which looks different to other marks on the skin, particularly if it changes over time.

The web page has photographs of normal moles, moles which are changing and melanomas to help individuals to learn how to examine their own moles.

Further information:

For further information, or requests to interview Professor Bishop, please contact Simon Jenkins, senior press officer at the University of Leeds, tel: 0113 3434031 (w) or 07791 333229 (m).

Notes to editors:

1. The paper Genome-wide association study identifies three loci associated with melanoma risk, is published in Nature Genetics. A copy of the paper is available on request.

2. Tim Bishop is Professor of Genetic Epidemiology, and Julia Newton-Bishop is Professor of Dermatology, in the Leeds Institute of Molecular Medicine at the University of Leeds.

3. The 2008 Research Assessment Exercise showed the University of Leeds to be the UK's eighth biggest research powerhouse. The University is one of the largest higher education institutions in the UK and a member of the Russell Group of research-intensive universities. The University's vision is to secure a place among the world's top 50 by 2015.

4. The Leeds Institute of Molecular Medicine (LIMM) is a research Institute of the University dedicated to defining the molecules involved in human diseases, and using this knowledge to develop novel therapies and new drugs.

5. Research by the Melanoma Genetics Consortium (GenoMEL) at Leeds brings together world-class expertise and a range of different disciplines to halt the rise of skin cancer. GenoMEL's focus is on genetics in relation to the incidence of melanoma, with a multi-national grouping of 23 different research capturing research and data from a range of latitudes, populations and climates. GenoMEL is coordinated by the University of Leeds.

6. The Cancer Research UK SunSmart campaign gives advice on exposure to Ultra Violet Radiation, either from sunbeds or the sun.

Simon Jenkins | EurekAlert!
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