UTHSC researchers to study how hormones impact melanoma risk

As the United States experiences a continuous increase in cases of melanoma, researchers from the University of Tennessee Health Science Center are beginning a study to determine whether sex hormones affect the risk of the deadly skin cancer.

The researchers have received a $423,500 grant from the National Institute of Environmental Health Sciences, part of the National Institutes of Health (NIH), to study the role of balanced sex hormones in DNA repair in human melanocytes. Feng Liu-Smith, PhD, associate professor in the College of Medicine’s departments of Dermatology and Preventive Medicine, is the principal investigator, Tejesh Patel, MD, chair of the Department of Dermatology, and Chi-Yang Chiu, PhD, associate professor of Preventive Medicine, are collaborators on the project.

Melanoma is a type of cancer that occurs in melanocytes, the cells that produce the pigment melanin in the skin, hair, and eyes. It appears most often on the skin, including areas not always exposed to sunlight, such as the soles of feet, palms of the hands, inside the mouth, and in the eyes. Studies have found skin cancer is the most common type of cancer in the United States, and while carcinoma is more common, melanoma is deadlier, claiming the lives of more than 7,000 people in the U.S. every year, according to the Melanoma Research Foundation.

“For other types of skin cancer, like squamous cell carcinoma or basal cell carcinoma, a simple surgery can be considered curative, but with melanoma, that’s not really the case,” Dr. Liu-Smith said. According to her, novel prevention methods may be needed to decrease the rate of cases and potentially save lives.

“Since the National Cancer Act of 1971, a lot of other cancer types show a decreasing trend, especially in recent years. Melanoma is one that continues to increase,” she said. “The only prevention we have is based on avoiding UV radiation—wearing sunglasses, wearing hats, wearing long sleeves, seeking shade.”

While these protections against environmental factors can be effective, Dr. Liu-Smith said researchers have wondered if there are additional risk factors, such as endogenous biological determinants, that may predispose someone to melanoma.

“Young women are at higher risk than young men, but as they age, the risk flips so older men actually have a much higher risk than older women. It’s a very intriguing observation from an epidemiology point of view, and I’m trying to understand why that happens,” Dr. Liu-Smith said.

Dr. Liu-Smith believes human sex hormones might play a part. “The main male sex hormone is testosterone, and the main female sex hormone is estrogen. But women also have high levels of testosterone—not as high as men—and that plays a very important role in physiology, pathology, and everything. Similarly, men also have estrogen, so my hypothesis is that the ratio of these two hormones is highly linked to the frequency of melanoma.”

To study this, volunteers will be recruited and given patches that stick to the skin and release testosterone into the body. The researchers will analyze samples of each volunteer’s skin to determine if there are any changes in how the person’s DNA repairs skin damage before and after the hormones were adjusted.

If there is a change after testosterone levels are raised, Dr. Liu-Smith said there are ways to modify sex hormone levels in everyday life to reduce the risk of melanoma. “Certain diets can change the ratio of sex hormones, so by eating different foods, we might be able to modify the sex hormone levels and make them more balanced. So, in that way, we may be able to have a new prevention method,” she said. “We don’t know what the ideal ratio is, but hopefully our study will give us a clue.”

Dr. Liu-Smith said she is grateful for the opportunity she has received through this NIH grant and is hopeful she and the research team will make findings that are useful for preventing melanoma cases and reducing deaths.