Researchers show why people with the greatest number of moles are at increased risk of the most dangerous form of skin cancer and identify the actual genes associated with this increased risk.

The study looked at more than 10,000 people, comparing those who have been diagnosed with melanoma to those who do not have this form of skin cancer a number of clear genetic patterns emerged.

Image: Part of the ABCDs for detection of melanoma. On the left side from top to bottom: melanomas showing (A) Asymmetry, (B) a border that is uneven, ragged, or notched, (C) coloring of different shades of brown, black, or tan and (D) diameter that had changed in size. The normal moles on the right side do not have abnormal characteristics (no asymmetry, even border, even color, no change in diametry).

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.

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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, study author. "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 color," 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 behavioral 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 skin 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.

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References:
1. Julia Newton Bishop and Tim Bishop, et al. Genome-wide association study identifies three loci associated with melanoma risk. Nature Genetics.

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