Increased Numbers of Nevi Can Predict Risk of Melanoma

BETHESDA, Md--Increased numbers of small nevi, large nondysplastic nevi,and clinically dysplastic nevi strongly increase a person's risk of developingmelanoma--a finding with major preventive implications, according to investigatorsin a large, case-control study.

"The clinical implications are that a clinician or health careprovider can establish the risk of melanoma by skin examination alone,"said Margaret A. Tucker, MD, of the National Cancer Institute's GeneticEpidemiologic Branch. She presented data from the study at the GeneralMotors Cancer Research Foundation's annual scientific conference held atthe National Institutes of Health.

Some 40,300 new melanoma cases will be diagnosed and 7,300 melanomadeaths will occur in the United States during 1997. The incidence of melanomahas continued to rise "dramatically since the 1930s," Dr. Tuckersaid.

The reason remains uncertain, but studies have linked increased sunexposure and the presence of nevi to the disease. However, few of theseepidemiologic studies successfully evaluated the relative contributionof small, large, and dysplastic nevi.

Researchers from NCI, the University of California, San Francisco, andthe University of Pennsylvania launched a major effort to sort out theissue. They enrolled 716 consecutive newly diagnosed melanoma patientsat the two medical schools during 1991 and 1992. These patients were matchedwith 1,014 controls randomly selected from outpatient clinics and matchedfor age, sex, race, and geographic distribution.

All study participants were interviewed and received complete skin examinations,including photographs of most atypical nevi and a biopsy of the most atypicalnevus, if they were willing. The criteria for a dysplastic nevi includeda size greater than 5 mm with a flat component and at least two of thefollowing characteristics: variable pigmentation, irregular outline, andindistinct borders.

Small Nevi Increase Risk Twofold

The researchers found that in patients without dysplastic nevi, increasednumbers of small nevi raised the risk of melanoma about twofold; increasednumbers of both small and large nondysplastic nevi raised the risk fourfold.

A single dysplastic nevus increased the melanoma risk twofold. Ten ormore dysplastic nevi shot the risk up 12-fold. Dr. Tucker noted that dysplasticnevi occur in about 10% of the US population. The study also showed thatcongenital nevi did not confer an increased risk, while freckling raisedthe risk twofold.

After adjusting for dysplastic nevi, total nevi, age, sex, freckling,and skin type, the team found that melanoma risk increased with the totalnumber of sunburns. One to three sunburns increased a person's risk 40%;10 or more burns nearly doubled the risk. "The risks were highestin those with both multiple dysplastic nevi and sunburns, a more than 20-foldincrease," Dr. Tucker said.

To the researchers' surprise, however, sunburns prior to age 13 didnot increase risk, a finding contrary to some other studies. "We founda small risk associated with early sun exposure, but it did not reach statisticalsignificance," she said.

Living in the tropics, using sunbeds or tanning booths, or working outdoorsdid not increase the risk of melanoma among the study participants.

"There are many people with an increased number of common neviwho are at a two- to fourfold increased risk of melanoma, and people withunusual nevi are at roughly a 10-fold increased risk," Dr. Tuckersaid.

Thus, she noted, a subset of patients can be identified who could benefitfrom surveillance, with early biopsy of dysplastic nevi, and intervention(warnings to stay out of the sun).

Said Dr. Tucker: "We know from our studies of familial melanomathat once we get people with this inherited predisposition out of the sun,their risk of developing melanoma drops substantially after five years."