Genetic Variants in Red Heads Increase Skin Cancer Risk


People with pale skin, freckles, and red hair carry mutations comparable to an extra 21 years of sun exposure.

Red-headed individuals are known to have an increased likelihood of developing skin cancer. But for the first time, a new study has proven that genetic variants associated with pale skin, freckles, and red hair are linked to a greater number of genetic mutations in skin cancer.

Globally, people with red hair account for between 1% and 2% of the world’s population, and about 6% of the UK population. They carry 2 copies of a variant of the MC1R gene, which affects the type of melanin pigment they produce.

These variants lead to red hair, pale skin, freckles, and the tendency to burn in the sun easily. In a study published in Nature Communications, researchers found that these genetic variants were linked to a larger number of genetic mutations in skin cancer that it is comparable to an extra 21 years of sun exposure.

“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,” said lead co-author David Adams. “Unexpectedly, we also showed 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. This is one of the first examples of a common genetic profile having a large impact on a cancer genome and could help better identify people at a higher risk of developing skin cancer.”

For the study, researchers analyzed publicly-available data sets of tumor DNA sequences from more than 400 people. The results showed an average of 42% more sun-associated mutations in tumors from people who carried the genetic variant.

“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,” said lead co-author Tim Bishop. “It has only been possible due to the large-scale data available. The tumors were sequenced in the USA, from patients all over the world and the data was made freely accessible to all researchers. This study illustrates how important international collaboration and free public access to data-sets is to research.”

Previously, it was thought that the type of skin pigment associated with red heads may allow more UV rays to reach the DNA. Although this may be a mechanism of DNA damage, findings from the study showed that the MC1R gene variation increased the amount of spontaneous mutations caused by ultraviolet light, in addition to increasing the level of other mutations in the tumors.

The findings suggest that the biological processes exist in cancer development in people who carry the MC1R variation that are not related to ultraviolet light solely.

“This important research explains why red-haired people have to be so careful about covering up in strong sun,” said Julie Sharp, head of health and patient information at Cancer Research UK. “It also underlines that is isn’t just people with red hair who need to protect themselves from too much sun. People who tend to burn rather than tan, or who have fair skin, hair or eyes, or who have freckles or moles are also at a higher risk."

Authors noted that everyone needs to protect their skin from the sun, and take preventive measures for skin cancer.

“For all of us the best way to protect skin when the sun is strong is to spend time in the shade between 11 am and 3 pm, and to cover up with a t-shirt, hat and sunglasses,” Sharp said. “And sunscreen helps protect the parts you can’t cover; use one with at least SPF15 and 4 or more stars, put on plenty and reapply regularly.”

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