Individuals with red hair have an increased risk of developing skin cancer. For the first time, however, researchers have ascertained the size of this risk. Surprisingly, the researchers also discovered that it is not just red-haired people who share the danger.
Exposing the skin to UV light, whether from the sun or a tanning bed, increases the risk of damaging DNA.
This interaction has been known for some time. However, not everyone's DNA is equally susceptible to UV's disruptive quality.
Individuals with red hair and fair skin are particularly sensitive to this type of damage.
Red-headed people make up around 1-2 percent of the global population but around 6 percent of British people.
These individuals carry two copies of a particular variant of the MC1R gene, which alters melanin pigment production, causing the development of pale skin, freckles, and red hair.
MC1R gene and sun damage risk
The MC1R gene codes for the melanocortin 1 receptor, which is involved in the production of the pigment, melanin. Melanin is essential for controlling pigmentation of the eyes, hair, and skin. There are two types of melanin - eumelanin, which produces dark hair and protects against UV rays, and pheomelanin, which does not protect cells from UV attack.
Mutations found in a redhead's MC1R gene reduce its ability to produce eumelanin; therefore, pheomelanin is produced in abundance, leaving the skin unguarded and at the mercy of the sun's rays.
Although individuals carrying two copies of the MC1R gene variant are known to have this particular susceptibility to sun damage, the exact size of this risk was not known. Investigators from the Wellcome Trust Sanger Institute set out to uncover the amount of risk involved in carrying two copies of this particular gene.
"It has been known for a while that a person with red hair has an increased likelihood of developing skin cancer, but this is the first time that the gene has been proven to be associated with skin cancers with more mutations."
Dr. David Adams, joint lead researcher
Researchers looked at databases of tumor DNA sequences from more than 400 individuals. The data came from patients all over the world and was sequenced in the United States. They found that people carrying the MC1R gene variant displayed 42 percent more sun-associated mutations in their tumors.
The level of mutations associated with the MC1R mutation were equivalent to an additional 21 years of sun exposure, compared with those who do not carry the variants.
Joint lead author Prof. Tim Bishop, director of the Leeds Institute of Cancer and Pathology at the University of Leeds, said: "This is the first study to look at how the inherited MC1R gene affects the number of spontaneous mutations in skin cancers and has significant implications for understanding how skin cancers form."
A new mechanism for skin cancer?
Previously, it was thought that the changes in skin pigment associated with being red-headed allowed more UV to reach the DNA and disrupt it. This may be the case, but the current findings demonstrate that there are other mechanisms at work.
The team found that the MC1R gene variant, as expected, increased the quantity of mutations caused by UV; but surprisingly, they found that levels of other, non-UV-related mutations rose, too. This implies that the MC1R variant might alter or interfere with other pathways that lead to tumor mutations.
These findings do not just affect red-haired individuals with two copies of the MC1R variant, they also impact people who do not display the red-haired traits, but who carry a single copy of the variant. According to Dr. Adams, they found that "people with only a single copy of the gene variant still have a much higher number of tumor mutations than the rest of the population."
These findings mark one of the first times that a common genetic profile has been shown to have a large effect on a cancer genome.
All of the data for this study was made freely available to all researchers and demonstrates the value of collaborative research and public access datasets. The team hopes that the results will help to identify people at risk of developing skin cancer more easily; they also hope that this type of data sharing brings new and exciting discoveries to the fore.