The Influence of Inherited Genes on Melanoma Risk

Most people associate skin cancer warnings with sunburn and tanning beds. “Cancer genes” or inherited risks are associated with diseases such as breast and colon cancer. A new study challenges the status quo by demonstrating that genetics have a more important influence on melanoma risk than previously thought.

Physicians seldom perform genetic screenings to determine risk factors for patients with a family history of melanoma since earlier, limited research shows that only 2–2.5% of instances are inherited. For the same reason, insurance companies seldom cover these tests unless in the most severe cases. In the medical industry, genetic testing is rarely provided for tumors that do not satisfy a 5% criterion.

A study headed by Cleveland Clinic's Joshua Arbesman, MD, and Stanford Medicine's Pauline Funchain, MD (previously Cleveland Clinic) reveals that melanoma exceeds that 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 between 2017 and 2020 had mutations in cancer risk genes. The study team which includes Ying Ni, PhD, of the Cleveland Clinic Center for Immunotherapy and Precision Oncology, and Claudia Marcela Diaz, PhD, examined worldwide patient databases and discovered similar findings. 

Hereditary cancers can wreak havoc through families and leave devastation in their wake. Genetic testing lets us proactively identify, screen, and even treat these families to equip them with the tools they need to get the best healthcare possible. 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 Joshua Arbesman, MD, Principal Investigator, Cleveland Clinic Lerner Research Institute

According to Dr Arbesman, who oversees the Cancer Biology lab at the Cleveland Clinic Lerner Research Institute, his results also corroborate a view that is becoming more and more common among cancer biologists: there are risk factors other than sun exposure that might affect a person’s likelihood of developing melanoma.   

Dr Arbesman added, “Not all of my patients had inherited mutations that made them more susceptible to the sun. There's something more going on here and more research is needed.”

Dr Arbesman and his colleagues are investigating several of the genes identified in his patients’ genetic testing to understand more about how melanoma arises and how it might be treated. For example, he is investigating whether some of his patients and their families with inherited mutations will benefit more from immunotherapy than those without inherited mutations. His group is also investigating how other individuals’ genes influenced the development and severity of their melanoma.

Source:
Journal reference:

Funchain, P., et al. (2024) Germline cancer susceptibility in individuals with melanoma. American Academy of Dermatology. doi.org/10.1016/j.jaad.2023.11.070

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