Red-hair gene tied to melanoma
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Red-hair gene tied to melanoma

It's no secret that fair-skinned redheads have a higher risk of melanoma. Now, an Australian group has identified the genetic link. People with dangerous variants of a gene called the melanocortin-1 receptor (MC1R) have at least double the risk of contracting skin cancer, even if they have medium or olive skin, researchers said here today. "The [variants] associated with red hair are the ones with greatly increased risk of melanoma," says Richard Sturm of the University of Queensland in Brisbane, Australia, lead author of the study. Redheads are known to have about a five times higher risk of melanoma than people with dark hair.

Although exposure to ultraviolet light places people at risk for melanoma, genetic factors also play a role. People face a high risk of melanoma if they have fair skin, red hair, blue eyes, freckles, or a tendency to react to sun by burning rather than tanning.

Sturm's group has spent the last few years trying to pinpoint the specific genes that underlie these risk factors. They focused on the MC1R gene because it varies greatly among Caucasians, he says, and because variants of the gene specify whether a person has red hair.

The type of MC1R gene a person carries also determines whether he or she produces the kind of melanin typical of fair-skinned people, called pheomelanin, or that typical of brown-skinned people, called eumelanin. "It's the gene that determines your tanning potential," Sturm says.

Because of the protective effects of eumelanin, dark-skinned peoples - such as African-Americans or Australian aborigines - generally do not develop melanoma, although they can develop other forms of skin cancer and other sun-induced skin damage such as premature aging.

In a small preliminary study, the Australian team examined 111 people at high risk and 109 people at low risk for three types of skin cancer. The researchers then checked to see which alleles of the MC1R gene were present. The results showed that the presence of any of the three alleles for red hair triple the risk of skin cancer and melanoma.

To confirm these results in a larger study, the Australian team tested for variants of the gene in 459 Australians with melanoma and 399 research participants who did not have melanoma.

People with one of the three dangerous MC1R variants were twice as common in the melanoma group as in the control group. People who were homozygous for the red-hair alleles had four times the incidence of having skin cancer as people with the wild-type MC1R gene. But even carriers with darker hair and medium or olive complexions had more than twice the risk of developing melanoma.

Sturm plans to develop a genetic test that could let people know their risk more accurately than a self-assessment of skin and hair color. Still, everyone, no matter what his or her genetic make-up, needs to limit sun exposure, Sturm says. "Anyone who thinks they're protected because they have a wild-type genotype is fooling themselves.


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