Belfast Telegraph

Saturday 25 October 2014

Red hair gene 'linked to melanoma'

Red-heads such as Julianne Moore are at greater risk of melanoma, research shows

Prince Harry, Mick Hucknall and Julianne Moore all share a deadly secret linked to their carroty locks.

The gene responsible for red hair also leaves a person up to 100 times more susceptible to the worst form of skin cancer, scientists have shown.

It was always known that fair-skinned red-heads are at greater risk of melanoma, which claims more than 2,000 lives a year in the UK. Now US researchers believe they have discovered why. A particular gene mutation that colours hair red leaves DNA in skin cells more prone to damage by sunlight.

Laboratory and mouse experiments showed that the MC1R-RHC gene variant both lowered a cell's guard against harmful ultraviolet (UV) rays, and stimulated cancer-causing biological signals. RHC stands for "red hair colour".

Study leader Dr Wenyi Wei, from Harvard Medical School in Boston, said: "Together, our findings provide a possible molecular mechanism as to why red-haired individuals harbouring MC1R mutations are much more susceptible to UV-induced skin damage than individuals with darker skin, resulting in a 10 to 100-fold higher frequency of melanoma."

Melanoma is diagnosed in about 13,000 people each year in the UK and is responsible for three quarters of all skin cancer deaths. The cancer originates in pigment-producing skin cells called melanocytes. Previous research had shown that the melanocortin-1 receptor (MC1R) gene plays a key role in protecting melanocytes from UV-induced DNA damage.

Under normal circumstances MC1R binds to and protects another gene well known for its ability to suppress tumours, PTEN. The new work demonstrates that the red hair version of MC1R no longer acts as a PTEN guardian. "As a result, upon UVB exposure, we saw an increased destruction of PTEN in the mutated pigment cells," said Dr Wei.

The same mutation was linked to the ramping up of a biological signalling pathway, P13K/Akt, implicated in a number of cancers, including breast, ovarian and lung. A further connection was found with a mutation in the BRAF gene found in 70% of human melanomas.

It all adds up to bad news for Prince Harry and others of his ilk. But the scientists say there is also a glimmer of light in the findings, reported online in the journal Molecular Cell. The research could open up avenues of study leading to new melanoma treatments or ways of identifying highly at-risk individuals. "We think that MC1R variants, in combination with mutations in the BRAF gene, could be used as markers of an increased risk of developing melanoma," said Dr Wei.

There was also a suggestion that compounds that inhibit P13K/Akt could be combined with the skin cancer drug vemurafenib to treat some melanomas.

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