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Even without sun, redheads may be at higher risk of melanoma

LOS ANGELES – Doctors have long urged people with red hair, fair skin and freckles to avoid the sun and its damaging ultraviolet rays. To venture outdoors without a wide-brimmed hat and sunscreen was simply courting skin cancer, they cautioned.

Now, however, a study in mice suggests that those among us with ginger hair and fair complexions face an elevated risk of the disease even when covered up.

The study, published online Wednesday in the journal Nature, suggests that the same reddish-yellow pigment that gives rise to rusty locks and an inability to tan is itself a potential trigger in the development of melanoma, the deadliest form of skin cancer.

The findings appear to solve the riddle of why darker-skinned individuals have a significantly lower risk of melanoma than lighter-skinned people, even when the sun protective factor, or SPF, of dark skin is just two to four levels higher than that of light skin.

“Even if you’re good about avoiding UV rays – you know, putting on sunscreen, wearing protective clothes and being careful at the beach – it’s still possible this red pigment is related to carcinogenic activity anyway,” said Dr. David E. Fisher, director of the melanoma program at Massachusetts General Hospital in Charlestown and senior author of the study.

Melanoma is a form of cancer that begins in the skin’s pigment-producing cells, or melanocytes, and is often associated with fair skin, excessive exposure to sunlight and tanning lamps, or a preponderance of moles. The National Cancer Institute estimates that more than 76,000 people will be diagnosed with melanoma in 2012 and that more than 9,000 will die from it.

The color of human skin, hair and eyes is dictated by two types of melanin pigment: pheomelanin, which is reddish-yellow, and eumelanin, which is brownish-black.

Initially, Fisher and colleagues set out to examine how moles can develop into melanoma when exposed to ultraviolet light, a form of radiation that can damage DNA. The test subjects were mice bred to be susceptible to cancer. Because mouse hair is also determined by eumelanin and pheomelanin, researchers used black, albino and golden-yellow – or “red-headed” – mice to mimic a range human pigmentation.

Yet even before researchers got a chance to expose the mice to UV rays, 50 percent of the redheads developed melanoma within a year. Their black and albino counterparts, however, developed melanoma at low rates and over a longer period.

“We were very surprised,” Fisher said. “In fact, one of the first things we did was go back into the animal room with a UV meter just to be sure that for some inexplicable reason the lights were not actually emitting ultraviolet radiation.”

Study authors surmised that the pheomelanin pigment itself was causing a damaging chemical reaction inside the animals’ skin cells. This damage, called oxidative stress, occurs when cells produce an altered type of oxygen molecule as waste. Normally, cells can protect against these waste molecules, but an overabundance can damage the cell and its DNA, possibly laying the foundation for cancer.

When researchers compared skin samples of the different mice, the redheaded mice showed almost three times as much damage due to oxidative stress, leading authors to conclude that pheomelanin was the culprit.