Study: Mutations in familial melanoma genes and cancer risk
Researchers studied nearly 700,000 people from the United States and the United Kingdom to learn how common mutations in familial melanoma genes are in the general population. They found that these mutations may be more common than previously estimated and were often found in people who developed melanoma at a young age or who had more than one melanoma. These findings suggest that some people with melanoma may benefit from discussing genetic counseling and testing with their healthcare provider. (posted 7/28/2026)
By: Piri Welcsh, PhD
Reviewed by: Michael R Sargen, MD
RELEVANCE
Most relevant for: People who may be at high risk for melanoma.
It may also be relevant for:
- people with a family history of cancer
Relevance: Medium-High
Strength of Science: Medium-High
Research Timeline: Post Approval
What is this study about?
This study looked at mutations that may increase a person’s risk of developing melanoma, a serious type of skin cancer. Researchers wanted to learn how often these gene changes are found among people in the general population, not just those who already had cancer or a strong family history of melanoma.
Why is this study important?
Most research on inherited melanoma risk has focused on people who already had melanoma or were from families with several cases of melanoma or other cancers. This makes it hard to know how common these mutations are in the broader population or how much they increase cancer risk for people without a strong family history.
This study used a different approach. Instead of focusing on people because of their cancer history, researchers looked for mutations in melanoma-related genes among nearly 700,000 people in two large population databases. They then linked this genetic information with cancer registry records to see which cancers people developed. They looked at:
- how often mutations in familial melanoma genes are found in people from the general population.
- whether people with these mutations had a higher risk of melanoma or other cancers.
- whether certain melanoma histories—such as melanoma before age 40 or more than one melanoma—may help identify people who would most benefit from genetic testing.
This approach may give a more realistic picture of melanoma risk than studies based only on high-risk families. The results may help experts refine recommendations for genetic testing and cancer risk counseling for people with melanoma or a family history of melanoma.
Study findings
Researchers analyzed data from nearly 700,000 people from two large health databases: 469,379 people from the United Kingdom. Biobank database and 227,286 people from the Geisinger MyCode database in the United States.
Researchers looked for mutations in eight genes known to be associated with hereditary melanoma: ACD, BAP1, , , MITF E318K, POT1, TERF2IP and TERT promoter.
Frequency of mutations in familial melanoma genes in the general population
Mutations in one of the eight genes were seen in:
- 1 in 212 (0.5%) people in the U.S. group.
- 1 in 113 (0.9%) people in the U.K. group.
The most common mutation was in the MITF gene, specifically MITF E318K (found in 1 in 129 individuals in the UK group and 1 in 244 individuals in the US group). Otherwise, individual mutations in each gene were rare in the general population—less than 1 in 1,500 individuals tested positive for each of the other seven genes.
Frequency of melanoma for individuals with a mutation
A total of 1,765 people in the U.S. group and 6,987 people in the U.K. group were diagnosed with melanoma.
Among people with a single diagnosis of melanoma:
- 32 of 1,552 (2.1%) in the U.S. group had a gene mutation.
- 152 of 6,198 (2.5%) in the U.K. group had a gene mutation.
Among people with two or more diagnoses of melanoma:
- 15 of 213 (7.0%) in the U.S. group had a gene mutation.
- 42 of 789 (5.3%) in the U.K. group had a gene mutation.
Among people who had their first diagnosis before age 40:
- 5 of 135 (3.7%) in the U.S. group had a gene mutation.
- 13 of 406 (3.2%) in the U.K. group had a gene mutation.
In clinical practice, genetic testing is often recommended for moderate and high-risk cancer genes when there is a >2.5% chance of having a mutation. Importantly, in this research, individuals who had more than one melanoma or were diagnosed before age 40 had a greater-than 2.5% chance of having a mutation. Therefore, anyone with those histories should review recommendations with their medical team and/or a genetics expert.
People with mutations in the gene or the MITF E318K mutation appeared to develop melanoma at younger ages than people without these mutations. This finding suggests that earlier skin cancer screening may be beneficial for some individuals and families.
Other cancer risks associated with familial melanoma gene mutations
Besides melanoma, the study was also able to confirm previously reported links between specific genes and other cancers:
- was associated with pancreatic, brain, and head and neck cancers.
- MITF E318K was associated with kidney cancer.
- POT1 was associated with thyroid and blood cancers.
The researchers also reported possible links to other cancers, including:
- BAP1 and cancer.
- CDNK2A and biliary tract, breast, nonmelanoma skin, and small intestine cancers.
- MITF E318K and cervical, nasal and middle ear, and nonmelanoma skin cancers.
- POT1 and multiple myeloma.
More research is needed to confirm these possible associations and determine how they may affect cancer risk.
This study found that mutations in genes linked to melanoma may be more common than once thought. Mutations in these genes may also be linked to other cancers, but more research is needed to understand those risks.
What does this mean for me?
The findings from this study suggest that genetic counseling or genetic testing could be beneficial for people with melanoma, especially people diagnosed at a young age or people diagnosed with more than one melanoma.
Genetic testing can provide helpful information about cancer risk, but results are not always straightforward. A genetic counselor can help explain what the result means, what screening or prevention steps may be appropriate and whether relatives should consider testing.
Reference
Goldstein AM, Kim J, Haley JS, et al. Prevalence of Familial Melanoma Genes and Cancer Risk Among Genomically Ascertained Individuals. JAMA Dermatol. Published online May 27, 2026.
Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.
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posted 7/28/2026
Questions To Ask Your Doctor
- Based on my personal and family history, should I consider genetic testing for hereditary melanoma?
- Would a referral to a genetic counselor be appropriate for me?
- Could a mutation in a melanoma gene also affect my risk for other cancers?
- Are there steps I should take now to lower my melanoma risk, regardless of whether I have genetic testing?
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