Current genetic research is bringing
to light a new concern for melanoma risk.
Research has shown for many years that
those with red hair, fair skin, freckles and an inability to tan may be at a
greater risk for developing melanoma. A
new study in mice, published in the journal Nature, suggests that even if they
never are in sunlight, they may be at an increased risk for melanoma due to
genetic factors. They have linked this
to a genetic mechanism that is also linked to fair coloring.
"We've known for a long time that
people with red hair and fair skin have the highest melanoma risk of any skin
type," study author Dr. David Fisher of Massachusetts General Hospital
said in a statement. "The risk for people with this skin type has not
changed, but now we know that blocking UV radiation -- which continues to be
essential -- may not be enough."
The study suggests that the key seems
to be the gene for the melanocortin 1 receptor, MC1R. The variations in the gene can lead to
different levels of two variants of melanin-- the
brown-black eumelanin and the red-yellow form, pheomelanin.
Named after the red color associated
with them, RHC polymorphisms were shown to lead to lower levels of eumelanin and
higher levels of pheomelanin. Pheomelanin is less able to protect against ultraviolet
light, which is at least part of the reason redheads have a higher risk of skin
cancer in general.
Fisher and colleagues noted that this
cannot be the whole answer for melanoma.
Unlike other skin cancers, melanoma can appear on skin that is not
exposed to sunlight. The mutations that
drive the disease have rarely been linked to UV damage. In order to dig deeper, the researchers
studied mice that were genetically identical with the exception of the MC1R
gene and produced relatively high levels of pheomelanin and another that had a
mutation that stopped pigment from being synthesized, although the MC1R gene
was normal.
The three strains were named after
their coat color: black, red and white.
They were crossed with mice that already expressed the BRafV600E gene,
one of the most common mutations in melanoma, in their pigment-producing
melanocytes. When kept from UV light
exposure, less than a quarter of the black and white mice showed signs of
melanoma. In contrast, half of the red
mice developed melanoma by the end the research. In other words, the mice with high levels of
pheomelanin (the red mice) were more likely to develop melanoma than those with
low or non-existent levels.
The researchers concluded that there
may be “intrinsic carcinogenic features” of pheomelanin synthesis and possibly
even the substance itself. They also
noted that “one possibility is damage caused by
reactive oxygen species, the researchers noted, since there is evidence that
pheomelanin amplifies ultraviolet-A-induced reactive oxygen species.”
They also cautioned that the study
does not “diminish the importance of sun exposure” as a factor that can
contribute to melanoma. Fisher suggested
that the findings may contribute to the development of better sunscreens and
other protective measures "that directly
address this pigmentation-associated risk while continuing to protect against
UV radiation."
According to Drs.
Meenhard Herlyn and Mizuho Fukunaga-Kalabis of the Wistar institute in
Philadelphia said that decreasing the risk is “perhaps the most pertinent
question.” They said that it is possible
that in black mice (and their human counterparts) the high levels of eumelanin
attacks the “reactive oxygen species” that are triggered by the pheomelanin. They argued in their accompanying piece that researchers
should consider topical compounds to increase eumelanin synthesis and even oral
antioxidants to see if this may decrease the risk of melanoma for red
heads. In the meantime, they suggest
that red heads continue to get regular check-ups and take precautions to
prevent cancer.
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