International study links 3 genes to melanoma

International study links 3 genes to melanoma

A consortium of European and Australian scientists doing a genome-wide association study found three gene variants were strongly linked to melanoma risk: two of them had previously been linked to pigmentation, freckling and sun sensitivity, and one was a new discovery. The findings may explain why people with the most moles on their skin have the highest risk of melanoma, the most dangerous form of skin cancer.

The study was led by Professors Julia Newton Bishop and Tim Bishop of the Melanoma Genetics Consortium (GenoMEL) at the University of Leeds and is published in the 5 July online issue of Nature Genetics.

For the study, they examined the genetic make up of more than 10,000 people, which meant looking at over 300,000 variants or "snips" (SNPs, single nuclotide polymorphisms) comparing those of people with melanoma to those who did not have the disease. They found a number of clear, genetic patterns.

Every year about 48,000 people worldwide die of melanoma, a disease responsible for most deaths from skin cancer. Many scientists suggest that the increase in melanomas in recent decades is partly due to the emergency of package holidays where people who don't get a lot of sun most of the year suddenly expose themselves to a lot of it for one or two weeks. They say intermittent, rather than daily exposure to the sun over longer periods puts people at higher risk of melanoma.

Also, it has already been shown that people who burn easily, have fair skin and red hair are most at risk of melanoma. The researchers found that the people in this study who had been diagnosed with melanoma were also more likely to be carrying genes that gave them red hair and freckles.

Tim Bishop, of the Leeds Institute of Molecular Medicine and the Cancer Research UK Centre at Leeds said this what they expected to find, but the links appeared much stronger than they anticipated.

"We had known for some time that people with many moles are at increased risk of melanoma," he said.

He and his colleagues found clear links between some genes on chromosomes 9 and 22 and increased risk of melanoma, but, as he explained:

"These genes were not associated with skin colour."

In fact, what they found, when they teamed up with colleagues at King's College London and in Brisbane, Australia, who had been counting moles on twins, was that:

"These genes actually influenced the number of moles a person has," said Bishop. However, we still don't know much about how sunshine and genetics come together to cause cancer in some people, he added, explaining that:

"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."

Bishop said what they did know was that the people most likely to develop melanoma were those with a particular combination of genes and a lifestyle of significant sun exposure.

Bishop and colleagues suggest there are five genes that influence melanoma risk and that a person with all five variants is about 8 times more likely to develop melonoma than a person with none, although most of us have at least one.

Cancer Research UK's director of health information, Sara Hiom, 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."

She said Bishop and colleagues had confirmed what Cancer Research UK, through its SunSmart campaign already advised: that people with lots of moles, and people with red hair and fair skin, are at higher risk of getting melanoma, and should take extra care in the sun. However, she added that:

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

"Genome-wide association study identifies three loci associated with melanoma risk."

D Timothy Bishop, Florence Demenais, Mark M Iles, Mark Harland, John C Taylor, Eve Corda, Juliette Randerson-Moor, Joanne F Aitken, Marie- Francoise Avril, Esther Azizi, Bert Bakker, Giovanna Bianchi-Scarrà, Brigitte Bressac-de Paillerets, Donato Calista, Lisa A Cannon-Albright, Thomas Chin-A-Woeng, Tadeusz De ogonbniak, Gilli Galore-Haskel, Paola Ghiorzo, Ivo Gut, Johan Hansson, Marko Hoc caronevar, Veronica Höiom, John L Hopper, Christian Ingvar, Peter A Kanetsky, Richard F Kefford, Maria Teresa Landi, Julie Lang, Jan Lubin acuteski, Rona Mackie, Josep Malvehy, Graham J Mann, Nicholas G Martin, Grant W Montgomery, Frans A van Nieuwpoort, Srdjan Novakovic, Håkan Olsson, Susana Puig, Marjan Weiss, Wilbert van Workum, Diana Zelenika, Kevin M Brown, Alisa M Goldstein, Elizabeth M Gillanders, Anne Boland, Pilar Galan, David E Elder, Nelleke A Gruis, Nicholas K Hayward, G Mark Lathrop, Jennifer H Barrett & Julia A Newton Bishop.

Nature Genetics, Published online: 05 July 2009


Additional source: University of Leeds.

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