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Pigment Gene Affects Risk for Melanoma
Melanomas are tumors that arise from the cells that produce skin pigment. While
not the most common type of skin cancer, they are the most serious. This year,
over 62,000 Americans are expected to be diagnosed with melanoma. Researchers
have now uncovered a complex interaction of two genes that dramatically affects
the chance of developing melanoma.
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| Melanoma under the microscope. Image from the Dr. Lance
Liotta laboratory, courtesy of NIH's National Cancer Institute. |
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The skin around melanomas often has the tell-tale wrinkly, thick appearance
brought on by damage from the sun. Ultraviolet radiation from the sun has many
effects on skin, including mutating, or changing, cancer-causing genes in skin
cells. But not all melanomas are found on skin with obvious chronic sun-induced
damage. One gene called BRAF seems particularly important for such melanomas.
Because melanomas on skin without obvious chronic sun-induced damage occur in
younger people and have frequent mutations in BRAF, researchers at NIH's National
Cancer Institute (NCI) hypothesized that people with these melanomas may have
inherited a gene that predisposes them to developing melanomas with BRAF mutations.
Caucasian people have a much higher chance than others of developing melanomas
on skin that's exposed to the sun, so the researchers thought that one candidate
might be the melanocortin-1 receptor (MC1R) gene, which is largely responsible
for differences in skin color, or pigmentation. Everyone has two copies of MC1R;
one from their mother and one from their father. Some variant forms are responsible
for traits such as fair skin, freckling and red hair. But MC1R may do much more
than influence pigmentation.
In a collaborative effort by scientists at NCI, the University of California
San Francisco and other institutes in the U.S. and Italy, researchers studied
the skin surrounding melanomas in 197 Caucasian people and identified those with
no or little signs of chronic sun damage. They then sequenced their MC1R genes
and BRAF genes from their tumor cells. For comparison, they analyzed the genes
in 171 healthy people.
The results were published online in Science on June 29. The non-chronic
sun-induced melanomas in people with at least one MC1R variant form had significantly
more frequent BRAF mutations. The risk for such melanomas with BRAF mutations
was seven times higher for people with one MC1R variant form, and 17 times higher
for those with two. In contrast, the people with MC1R variant genes but normal
BRAF genes had no higher melanoma risk.
This study shows that MC1R affects melanoma susceptibility in Caucasians by
affecting how vulnerable BRAF is to mutation. However, exactly how this relationship
works isn't known. Drugs targeting BRAF for melanoma are now in clinical trials.
Understanding how other factors like MC1R affect the development of BRAF mutations
may help researchers to develop new prevention and therapeutic strategies.
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