New skin cancer genes uncovered
Australian Broadcasting Corporation
Posted: Oct 11, 2011 10:06 AM ET
Last Updated: Oct 11, 2011 12:02 PM ET
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Four genes increase the melanoma risk, two studies at opposite sides of the globe have unearthed.
The discoveries may help to unravel how the deadly skin cancer develops, and could eventually lead to better treatments for the cancer. Both studies are reported in this week's Nature Genetics. 
Earlier genetic discoveries in melanoma related to skin pigmentation and moles. Mary Godleski/Associated Press
The studies compare the DNA of people who have melanoma with that of similar people who don't have the disease.
The Australian study, led by Dr. Stuart MacGregor of the Queensland Institute of Medical Research looked at 2,168 Australians with melanoma. Meanwhile Professor Tim Bishop of the University of Leeds led the UK study, which scrutinized the DNA of 2,981 people with melanoma in Europe.
Because melanoma is predominantly a disease of fair-skinned people, only people of European ancestry were included in the analysis.
Both teams were looking for variations in very short sections of DNA known as SNPs, which may point to different variants of the gene that the SNP is part of. The aim is to find SNPs, and hence gene variants, that correlate with having melanoma.
"We looked at about half a million SNPs," says MacGregor. "Because you are testing so many, you find lots that just look significant by chance."
Each team then used the other's data set to check that they really had detected SNPs that were related to melanoma. Four of the SNPs turned up as significant in both data sets.
Other susceptibility factors for melanoma
These four SNPs are in addition to at least seven others related to melanoma found in earlier genetic studies. These earlier SNPs relate to skin pigmentation and moles, which is significant as many melanomas start from an abnormal mole.
The next step was to work out which gene each SNP was part of. MacGregor's group, who found one of the SNPs, believe it is part of a gene known to caused melanoma in zebrafish.
Bishop's team found three SNPs. They think one of them lies in a gene that is important for DNA repair in the body.
"Because our skin is exposed to so much UV radiation, which damages DNA, anything likely to repair that damage would be a natural candidate," says Bishop.
The second SNP's gene has a role in programmed cell death (apoptosis) and is implicated in other cancers, including breast cancer. The third is more of a mystery: it is best known for being involved in extreme drowsiness. Bishop jokes that it may have something to do with people falling asleep in the sun.
"The interesting thing about the current study is that these new SNPs are not associated with either skin pigmentation or mole counts," says Bishop. "It suggests that there are other factors in susceptibility to melanoma that we don't understand yet. The challenge is to work out what these genes are doing."
Professor Ian Olver, CEO of the Cancer Council of Australia, says it isn't surprising that so many genes have an influence on melanoma.
"Cancers seem to require several genetic alterations before you actually trigger the cancer," says Olver. "Most cancers are going to be a combination of a genetic predisposition and environmental factors."
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