Sun exposure has long been viewed as the primary risk factor for skin cancer, with inherited genes playing a relatively minor role. But a new study challenges that conventional wisdom, finding that up to 15% of melanoma patients carry inherited mutations that predispose them to the disease.
The research, published in the Journal of the American Academy of Dermatology, suggests that family history and genetic testing should be given much more weight in assessing melanoma risk and determining which patients may benefit from enhanced screening and preventive measures.
“Hereditary cancers can wreak havoc through families and leave devastation in their wake,” said Dr. Joshua Arbesman in a press release. He is a melanoma researcher at Cleveland Clinic's Lerner Research Institute and led the study. “Genetic testing lets us proactively identify, screen and even treat these families to equip them with the best healthcare possible.”
The study analyzed genetic data from over 400 melanoma patients treated at Cleveland Clinic between 2017 to 2020. It found that 15.3% carried inherited mutations in genes known or suspected to increase cancer risk, such as BRCA2, BAP1, and TP53. Nearly half of the patients assessed had mutations impairing DNA repair mechanisms.
“I would recommend physicians and insurance companies expand their criteria when it comes to offering genetic testing to individuals with family histories of melanoma, because inherited predisposition to it isn't nearly as rare as we think it is,” Dr. Arbesman said.
The findings were further validated by analyzing three other datasets, which showed inherited mutation rates of 10.6% to 15.8% among melanoma patients.
Previous studies had estimated only 2 to 2.5% of melanoma cases were inherited, leading to genetic testing being rarely recommended outside extreme family histories. But Dr. Arbesman said his research supports a growing view that non-sun factors contribute substantially to melanoma risk.
“Not all of my patients had inherited mutations that made them more susceptible to the sun,” he said. “There's clearly something more going on here and more research is needed.”
His team is now studying how specific mutations increase melanoma risk and whether they impact treatment responses such as immunotherapy. Unravelling melanoma's genetic underpinnings could unlock new prevention and treatment strategies, Dr. Arbesman said.