Environmental Factor

Environmental Factor

Your Online Source for NIEHS News

August 2016

Skin cancer risk depends on trigger for DNA repair

People with fair skin are known to have higher risk for sunburn and skin cancer, but people with darker coloring can also be at risk, according to NIEHS-funded researcher Zalfa Abdel-Malek, Ph.D. In a July 21 seminar at NIEHS, Abdel-Malek explained that a key determinant of skin cancer risk is whether skin cells are triggered to repair DNA damage that occurs after sun exposure.

Abdel-Malek, professor of dermatology, and of cancer and cell biology, at the University of Cincinnati, said that this response depends on the melanocortin 1 receptor (MC1R), located on skin cells called melanocytes. She explained that melanocytes produce skin pigment, or melanin, both in fixed amounts and after exposure to the sun’s ultraviolet (UV) rays. But first, and even more importantly, they reduce the formation of DNA damage from UV exposure. If the MC1R isn’t fully functioning, DNA repair is reduced, and cells that fail to repair damaged DNA can multiply and become cancerous.

Discovering the role of MC1R in this process was a major breakthrough in understanding why skin cancer risk varies, according to Abdel-Malek. Unfortunately, loss or partial loss of MC1R function can be common, she said, occurring in at least 50 percent of the white population in the U.S., and sometimes in people with darker skin.

Clues from the MC1R gene

Abdel-Malek’s lab looks at a person’s MC1R gene to determine if the receptor will be fully functional, and, thus, whether the person may be less susceptible to skin cancer. She says the information provided by the gene is much richer than what we can tell from physical attributes, like fair skin.

“The MC1R gene, which regulates the diversity of human pigmentation, has over 200 variants,” she said. “But only three variants are strongly associated with very lightly pigmented skin, red hair, and poor tanning ability, and therefore, also with increased risk of melanoma and other forms of skin cancer.”

Yet many people carry these gene variants without having the obvious physical traits, she explained. Population studies have shown that these carriers are also more susceptible to skin cancer, especially when they also carry a mutation in a separate melanoma gene called CDKN2A. This knowledge has helped cell biologists better understand the MC1R.

(Virginia Guidry, Ph.D., is a technical writer and public information specialist in the NIEHS Office of Communications and Public Liaison and a regular contributor to the Environmental Factor.)


What happens after UV exposure damages DNA in skin cells?

Abdel-Malek says there are generally three possibilities.

  1. Cell growth is halted so DNA repair can occur.
  2. DNA damage is so extensive that cell death is triggered, for example, peeling after a bad sunburn.
  3. Cells survive with significant DNA damage that can persist when cells grow and divide.

The last outcome is the worst, because it increases the chance of DNA mutations that can lead to skin cancer. According to the National Cancer Institute, melanoma is the most deadly form of skin cancer and the rate of new cases has been increasing in recent decades.

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