What is familial malignant melanoma?
Familial malignant melanoma is a term usually referring to families in which two or more first-degree relatives (parent, sibling, or child) have melanoma. Overall, about 8% of people newly diagnosed with melanoma have a first-degree relative with melanoma. A much smaller percentage, about 1%, have three or more close relatives with melanoma.
Dysplastic nevi are large, flat, irregular, asymmetric, variably pigmented moles. They occur primarily on sun-exposed skin, but they also occur in areas that are not exposed to the sun. Individuals in melanoma-prone families frequently have these moles. The moles must be monitored very carefully for any change in size, shape, and color. In the United States, the average age for melanoma to be diagnosed in people with familial melanoma is in the 30s; the average age that melanoma is diagnosed in the general population is in the 50s.
What causes familial melanoma?
Familial melanoma is a genetic condition. This means that the risk of melanoma can be passed from generation to generation in a family. To date, two genes have been linked to familial melanoma. They are called CDKN2A and CDK4. A mutation (alteration) in one of these genes gives a person an increased risk of melanoma. However, alterations in these two genes only account for a small percentage of familial melanoma.
CDKN2A is unusual in that it affects two separate proteins that have different functions. One is called p16 and one is called p14ARF. Both CDKN2A and CDK4 play important roles in controlling when cells divide. Studies of families with mutations in CDKN2A from Europe, North America, and Australia have shown that the risk of melanoma varies by geographic area. The reasons for these differences are not fully understood. There may be differences in the amount of sun they receive, or other individual or genetic differences, or a combination of these factors.
Within melanoma-prone families with known mutations in both France and the United States, dysplastic nevi and sun exposure are independent risk factors for melanoma.
There is also growing evidence that variations in another gene, MC1R, alter risk of melanoma both in individuals with CDKN2A mutations and in individuals without CDKN2A mutations. MC1R is important in regulating pigment; variations have been associated with freckling and red hair.
Scientists believe that there are other genes not yet identified that also increase the risk of melanoma. Research is ongoing to learn more about familial melanoma.
How is familial melanoma susceptibility inherited?
Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. Familial melanoma susceptibility follows an autosomal dominant inheritance pattern, which means a mutation happens in only one copy of the gene. This means that a parent with a gene mutation may pass along a copy of his or her normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.
How common is familial melanoma?
Most cases of melanoma are sporadic (occurs by chance). The number of people who have an inherited risk of melanoma is unknown, but the number is thought to be low. It is estimated that about 8% of people with melanoma, have a first-degree relative with melanoma and only 1% to 2% of people with melanoma have two or more close relatives with melanoma.
How is familial melanoma diagnosed?
Familial melanoma is suspected when two or more close relatives have invasive melanomas (melanoma that has spread). In areas of higher sun exposure, like the southern United States or Australia, the frequency of sporadic melanoma is higher, so familial melanoma is not considered unless three or more close relatives have invasive melanoma. Familial melanoma may also be suspected if a single family member has multiple melanomas.
Genetic testing for mutations in the CDKN2A gene is commercially available. However, genetic test results are unlikely to change screening recommendations or clinical care for people who have had melanoma or people who have a strong family history of melanoma. Most families with familial melanoma will not have a mutation identified.
What are the estimated cancer risks associated with familial melanoma?
A person with a hereditary risk of melanoma has a greatly increased risk of developing melanoma during his or her lifetime.
There is also an increased risk of pancreatic cancer in families with familial melanoma and CDKN2A mutations, but this is relatively rare. Astrocytoma (a type of brain cancer) has also been reported in a few families.
What are the screening options for familial melanoma?
Anyone with a parent, sibling, or child who has had invasive melanoma should be carefully screened. Thorough skin screening should be performed every three to six months by a dermatologist, a nurse specializing in dermatology, or another specially trained health care provider (a doctor who specializes in skin problems) to monitor any pigmented lesions. It is important to watch moles closely for any signs of change in shape, size, or color. Taking pictures of moles may be helpful to show changes over time. Any suspicious moles or other skin changes should be removed by a doctor.
In families known or strongly suspected to have familial melanoma, children should begin screening by age 10. Family members should also perform regular self-examinations to look for skin changes. Due to the high risk of multiple melanomas, people with familial melanoma should avoid sun exposure and protect their skin when outside.
Screening recommendations may change over time as new technologies are developed, and more is learned about familial melanoma. It is important to talk with your doctor about appropriate screening tests.
Learn more about what to expect when having common tests, procedures, and scans.
Questions to ask the doctor
If you are concerned about your risk of melanoma, talk with your doctor. Consider asking the following questions of your doctor:
- What is my risk of melanoma?
- What can I do to reduce my risk of cancer?
- What are my options for cancer screening?
If you are concerned about your family history and think that you or other family members may have familial melanoma, consider asking the following questions:
- Does my family history increase my risk of melanoma?
- Should I meet with a genetic counselor?
- Should I consider genetic testing?
Additional resources
Guide to Melanoma
The Genetics of Melanoma
What to Expect When You Meet With a Genetic Counselor
National Cancer Institute
www.cancer.gov
American Cancer Society
www.cancer.org
CancerCare
www.cancercare.org
To find a genetic counselor in your area, ask your doctor or visit these websites:
National Society of Genetic Counselors
www.nsgc.org
National Cancer Institute: Cancer Genetics Services Directory
www.cancer.gov/search/geneticsservices
