SkinCancerNet Article
Genetic Testing for Melanoma has Limits

With the availability of genetic testing for melanoma, the deadliest form of skin cancer, you may be wondering if you should be tested. Many people say that if the results showed a higher-than-average risk, they would do more to protect their skin. Dermatologists caution that we should not rely on genetic testing alone. Here’s why.

Result Does Not Change Dermatologists’ Recommendations
Long before genetic testing, dermatologists recommended the following:

  1. Get regular skin cancer screenings

  2. Learn how to perform skin self-exams and examine your skin regularly

  3. Protect your skin from the sun — and do not use tanning beds or sun lamps

This advice does not change with the availability of genetic testing for melanoma. That’s right. If genetic testing shows an increased risk, your dermatologist will recommend the above. If genetic testing does not indicate an increased risk, your dermatologist will still recommend these practices. No one is immune to developing skin cancer. The first two practices help find skin cancers, including melanoma, early when treatment is most effective. The latter reduces your risk of developing skin cancer.

CDKN2A Gene Mutations Rare
Today’s commercially available genetic test for melanoma looks for gene mutations (changes) on a single gene called CDKN2A. Having these mutations increases a person’s lifetime risk of developing melanoma by an estimated 67% to 76%.

While this may tempt you to have the test, it is important to know that the likelihood of having these mutations is rare. Only about 1% of patients who develop a single, primary melanoma test positive for CDKN2A. As such, dermatologists typically recommend genetic testing for a small group of patients who have other select risk factors.

Melanoma has Many Risk Factors
Having certain mutations on the CDKN2A gene is but one risk factor. Many other risk factors increase the likelihood of developing melanoma. Excessive sun exposure, a previous skin cancer, having many moles or atypical moles, and a history of blistering sunburns are a few. A person may have all of these and have a negative CDKN2A test. If this is the case, the person’s still has a greatly increased risk of developing melanoma.

Test Result Could Give False Sense of Security
If the result is negative, this could give you a false sense of security. It is important to know that a negative test does not mean that you will not develop melanoma. Only a small percentage of people who develop melanoma have the CDKN2A mutations.

Research shows that lifestyle accounts for much of our susceptibility to diseases. And experts agree that what causes melanoma is complex.
This means that you still need to protect your skin from the sun and avoid tanning beds. Regular screenings and skin self-exams are important, too.

More Research Needed
The commercially available genetic test for melanoma is helpful for a select group of patients. Researchers continue to look for other genes that may play a role in melanoma. They also are looking at our SNPs, which is short for “single nucleotide polymorphisms.” Called “snips,” these are slight variations in our DNA that create our differences in appearance and how we develop diseases.

One variation that may increase our risk for melanoma is MDM2 SNP309. Studies of MDM2 SNP309, however, show differing results.

Another gene being studied is MC1R. One study found that people who have dark hair, suntan easily, and carry a variant on the MC1R gene have an increased risk of developing melanoma. Interestingly, this same study found that people who had this MC1R variant and red or blond hair did not have an increased risk of developing melanoma.

Recent genetic studies also uncovered the genes responsible for sun sensitivity, red hair, and freckling. While dermatologists have long known that people who have these characteristics have an increased risk of melanoma, they did not know what genes caused this.

Further research may identify more genes that can contribute to melanoma. Research also may lead to breakthroughs in the treatment of advanced melanoma.

Related Information
Risk Factors: Melanoma

Aspinwall LG, Leaf SL, Dola ER et al. “CDKN2A/p16 genetic test reporting improves early detection intentions and practices in high-risk melanoma families.” Cancer Epidemiol Biomarkers Prev 2008; 17: 1510-9.

Aspinwall LG, Leaf SL, Kohlmann W et al. “Patterns of photoprotection following CDKN2A/p16 genetic test reporting and counseling.” J Am Acad Dermatol 2009.

Firoz EF, Warycha M, Zakrzewski J et al. “Association of MDM2 SNP309, age of onset, and gender in cutaneous melanoma.” Clin Cancer Res 2009; 15: 2573-80.

Nan H, Qureshi AA, Hunter DJ et al. “A functional SNP in the MDM2 promoter, pigmentary phenotypes, and risk of skin cancer.” Cancer Causes Control 2009; 20: 171-9.

Shekar SN, Duffy DL, Youl P et al. “A Population-Based Study of Australian Twins with Melanoma Suggests a Strong Genetic Contribution to Liability.” J Invest Dermatol 2009. Apr 9. [Epub ahead of print]

Tsao H, Zhang X, Kwitkiwski K et al. “Low prevalence of germline CDKN2A and CDK4 mutations in patients with early-onset melanoma.” Arch Dermatol 2000; 136: 1118-22.

U.S. Department of Health and Human Services. “Genes Hike Melanoma Risk Even in Those Who Tan Well.” News release issued April 21, 2009. Last accessed April 22, 2009.

Vourc'h-Jourdain M, Volteau C, Nguyen JM et al. “Melanoma gene expression and clinical course.” Arch Dermatol Res 2009 March 27. [Epub ahead of print]

All content solely developed by the American Academy of Dermatology

Genetic testing for melanoma currently shows mutations on one gene. While these mutations greatly increase the risk of developing melanoma, the test cannot predict whether or not a person will get melanoma nor can it diagnose melanoma.





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Page last updated 5/13/09

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