Sun exposure, family history guide risk assessment for melanoma screening

Issue: May 10, 2014

NEW YORK — Several factors can help better define individuals at high risk for melanoma, according to a presenter at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

Those factors include sun exposure, family history, use of indoor tanning devices, hair color, skin color, and the presence of both benign and atypical moles, according to Hensin Tsao, MD, PhD, director of the melanoma genetics program and clinical director of the Melanoma and Pigmented Lesion Center at Massachusetts General Hospital.

Hensin Tsao

Tsao used those criteria to establish the following risk-assessment guide for patients:

Individuals at elevated risk include those with sun sensitivity or sunburn history, freckling, prior diagnosis of non-melanoma skin cancer, tanning bed use, immunosuppression or Parkinson’s disease. These patients should undergo annual skin checks, possibly alternating between a dermatologist and primary care provider, Tsao said.
Individuals at moderately elevated risk include those who have one family member with melanoma, those diagnosed with prior melanoma, and those with sporadic dysplastic nevi or multiple benign moles. They should undergo follow-up every 6 to 12 months.
Individuals at greatly elevated risk include those in a hereditary melanoma family and those with atypical moles. They should undergo follow-up every 3 to 6 months, Tsao said.

Tsao outlined several of the risk criteria during his presentation.

Sun exposure, burn history

“Sunburn overall is our biggest indicator,” Tsao said. “It’s the question we ask all of our patients: Have you had sunburns? If so, how many, and were they blistering? If their answer is yes, the burns usually occurred prior to age 18.”

Sunburn history doubles risk for melanoma and is the greatest sun-related risk factor, Tsao said.

A meta-analysis by Gandini and colleagues demonstrated total sun exposure was associated with a 34% increased risk for melanoma. Intermittent sun exposure was associated with a 61% increased risk, but researchers observed no statistically significant association between chronic sun exposure and melanoma risk.

“It’s possible these studies were really small and unstable, so they didn’t pick up a small signal,” Tsao said. “It’s also possible that those individuals who work outdoors chronically were selected for being nonburners and, therefore, were at lower risk, so there is the potential for that confounding effect.”

Indoor tanning

A systematic review conducted by an International Agency for Research on Cancer working group demonstrated sunbed use was associated with a 15% increased risk of melanoma. The group subsequently classified UV-emitting tanning devices as a Group 1 radiation device, meaning they are carcinogenic to humans.

A survey of white female high school students published last year in JAMA Internal Medicine revealed 15% of girls aged 14 years or younger had tanned indoors. The usage rate increased to about 40% among girls aged 17 or 18 years, and about one-quarter of girls in that age bracket reported high frequency of indoor tanning, defined as more than 10 times per year.

Survey participants who reported tanning indoors were more likely to engage in other high-risk behaviors, including binge drinking, illegal drug use, unhealthy weight control practices, history of sexual intercourse and multiple sexual partners.

“Routine sunscreen use and consumption of five or more fruits and vegetables per day were negative predictors for tanning bed use,” Tsao said. “This reflects a ‘high-risk’ pattern of behavior among users of sun lamps.”

Family history

About 5% to 10% of patients with melanoma report a family history of the disease. However, family history often is not validated due to the high percentage of false-positives and confusion between carcinomas and melanomas.

A meta-analysis showed family history was associated with a 74% risk of melanoma, with some studies suggesting the risk is greater if the melanoma developed in a first-degree relative.

The increased risk is attributed to a mix of shared traits (eg, fair skin), heredity and behavioral risk.

“The family that sunburns together often gets melanoma together,” Tsao said. “This does not imply that an autosomal dominant melanoma risk mutation is being transmitted.”

Genetic testing is an option, but without testing affected individuals in the kindred, it often does not make sense to test unaffected individuals. For those interested in genetic testing, the most important component is the genetic counseling, Tsao said.

Tsao also described the “push and pull” of genetic counseling.

The “push” for information must include understanding of the basic tenets of genetics, all genes known to influence risks, environmental influences, the potential results and clinical implications, and the availability of testing and insurance coverage.

“The information ‘pull’ also is very critical,” Tsao said. “We must ask patients, ‘Why do you want to know your genotype, and how would it change what you do? If the result is normal and they’re just going to go back to the tanning beds, that’s the wrong answer. That’s not a good reason to test them. What is the point of knowing your genotype if you’re going to continue to do the exact same thing?”

Skin phenotype

A study by Gandini and colleagues demonstrated a twofold melanoma risk for individuals with light skin compared with dark skin, those with sun-sensitive skin compared with those who do not, and those with high-density freckling.

It also showed a 78% increased risk for individuals with light hair color and a 62% increased risk for those with fair eye color.

History of NMSC

A study by Marghoob and colleagues suggested risk for melanoma was 17 times greater among individuals previously diagnosed with basal cell carcinoma or squamous cell carcinoma.

A study by Lindelof and colleagues suggested the risk for melanoma after basal cell carcinoma diagnosis increased 6.8-fold among men and 4.2-fold among women.

Presence of moles

A meta-analysis published in 2005 in the European Journal of Cancer suggested the presence of common benign moles increased melanoma risk by about 19%.

The risk increased as the number of common moles on the entire body increased:

0 to 15 moles, RR=1;
41 to 60 moles, RR=2.24 (95% CI, 1.9-2.64);
81 to 100 moles, RR=4.74 (95% CI, 3.44-6.53); and
101 to 120 moles, RR=6.89 (95% CI, 4.63-10.25).

The analysis, which included 13 case-control studies, showed melanoma risk increased as the number of common moles on the arms increased. Researchers calculated RRs of 1.44 (95% CI, 1.29-1.6) for those with one to five moles on their arms, 2.48 (95% CI, 1.9-3.23) for those with five to 10 moles; and 4.82 (95% CI, 3.05-7.62) for those with 11 to 15 moles.

The results also suggested a person with atypical moles is at roughly twice the risk for melanoma. The studies included in the analysis demonstrated an RR of 6.36 (95% CI, 3.8-10.33) for a person with five atypical nevi.

For more information:

Tsao H. Defining high-risk populations for melanoma risk and screening. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 11-12, 2014; New York.
Gandini S. Eur J Cancer. 2005;41:28-44.
Gandini S. Eur J Cancer. 2005;41:45-60.
Gandini S. Eur J Cancer. 2005;41:2040-2059.
Guy GP Jr. JAMA Intern Med. 2013;173:1920-1922.
International Agency for Research on Cancer Working Group on artificial ultraviolet light and skin cancer. Int J Cancer. 2007; 120:1116-1122.
Lindelof B. J Am Acad Dermatol. 1991;25:245-248.
Marghoob AA. Cancer. 1995;75:707-714.

Disclosure: Tsao reports consultant roles with Quest Diagnostics and SciBASE, and funding from the American Skin Association, the Department of Defense, the NIH and Piramal.