Inherited genes play a larger role in melanoma risk than previously thought

When it comes to skin cancer, most people think of warnings about sunburn and tanning beds. Thoughts of "cancer genes" or inherited risks are more often associated with diseases such as breast or colon cancer. A new study challenges this status quo, showing that genetics play a larger role in the risk of melanoma than is recognized.

Doctors rarely order genetic screenings to assess risk factors in patients with a family history of melanoma because previous limited research suggests that only 2% to 2.5% of all cases are genetic. For this same reason, insurance companies rarely cover these tests outside of the most extreme situations. In the medical field, genetic testing is not typically offered for cancers that do not meet the 5% threshold.

The study, conducted by a team of researchers and clinicians led by Joshua Arbesman, MD, of the Cleveland Clinic, and Pauline Funchin, MD, of Stanford Medicine (formerly of the Cleveland Clinic), suggests that melanoma more than meets this threshold. Their findings, published in the Journal of the American Academy of Dermatology, show that up to 15% (1 in 7) of patients diagnosed with melanoma by Cleveland Clinic physicians during the from 2017 to 2020, carried mutations in genes predisposing to cancer. The research team, including Cleveland Clinic Institute for Immune Therapeutics and Precision Oncology, Ying Ni, PhD, and Claudia Marcela Diaz, PhD, analyzed international patient databases and found similar results.

"Hereditary cancers can wreak havoc on families and leave devastation in their wake. Genetic testing allows us to proactively identify, screen and even treat these families, giving them the tools they need to receive the best care possible," says Dr. Arbesman. “I would encourage doctors and insurance companies to broaden their criteria when offering genetic testing to people with a family history of melanoma, because hereditary predisposition to melanoma is not as rare as we think.”

Dr. Arbesman, who directs a laboratory at the Cleveland Clinic's Lerner Institute for Cancer Biology, also says his findings support an increasingly popular belief among cancer biologists: There are risk factors other than sun exposure that may influence the likelihood of developing melanoma. In humans.

"Not all of my patients had inherited mutations that made them more vulnerable to the sun," he says. "There's clearly something else going on here and more research is needed."

Dr. Arbesman and his team are studying many of the genes identified in his patients' genetic tests to learn more about how melanoma develops and how it can be treated. For example, he is working to determine whether some of his patients and their families who have inherited mutations may benefit more from immune therapy compared with those who do not have inherited mutations. His lab is also working to determine how other patients' genes contributed to the development and severity of their melanoma.