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.