BETHESDA, Md--Increased numbers of small nevi, large nondysplastic nevi, and clinically dysplastic nevi strongly increase a person's risk of developing melanoma--a finding with major preventive implications, according to investigators in a large, case-control study.
"The clinical implications are that a clinician or health care provider can establish the risk of melanoma by skin examination alone," said Margaret A. Tucker, MD, of the National Cancer Institute's Genetic Epidemiologic Branch. She presented data from the study at the General Motors Cancer Research Foundation's annual scientific conference held at the National Institutes of Health.
Some 40,300 new melanoma cases will be diagnosed and 7,300 melanoma deaths will occur in the United States during 1997. The incidence of melanoma has continued to rise "dramatically since the 1930s," Dr. Tucker said.
The reason remains uncertain, but studies have linked increased sun exposure and the presence of nevi to the disease. However, few of these epidemiologic studies successfully evaluated the relative contribution of small, large, and dysplastic nevi.
Researchers from NCI, the University of California, San Francisco, and the University of Pennsylvania launched a major effort to sort out the issue. They enrolled 716 consecutive newly diagnosed melanoma patients at the two medical schools during 1991 and 1992. These patients were matched with 1,014 controls randomly selected from outpatient clinics and matched for 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 atypical nevus, if they were willing. The criteria for a dysplastic nevi included a size greater than 5 mm with a flat component and at least two of the following characteristics: variable pigmentation, irregular outline, and indistinct borders.
Small Nevi Increase Risk Twofold
The researchers found that in patients without dysplastic nevi, increased numbers of small nevi raised the risk of melanoma about twofold; increased numbers of both small and large nondysplastic nevi raised the risk fourfold.
A single dysplastic nevus increased the melanoma risk twofold. Ten or more dysplastic nevi shot the risk up 12-fold. Dr. Tucker noted that dysplastic nevi occur in about 10% of the US population. The study also showed that congenital nevi did not confer an increased risk, while freckling raised the risk twofold.
After adjusting for dysplastic nevi, total nevi, age, sex, freckling, and skin type, the team found that melanoma risk increased with the total number of sunburns. One to three sunburns increased a person's risk 40%; 10 or more burns nearly doubled the risk. "The risks were highest in those with both multiple dysplastic nevi and sunburns, a more than 20-fold increase," Dr. Tucker said.
To the researchers' surprise, however, sunburns prior to age 13 did not increase risk, a finding contrary to some other studies. "We found a small risk associated with early sun exposure, but it did not reach statistical significance," she said.
Living in the tropics, using sunbeds or tanning booths, or working outdoors did not increase the risk of melanoma among the study participants.
"There are many people with an increased number of common nevi who are at a two- to fourfold increased risk of melanoma, and people with unusual nevi are at roughly a 10-fold increased risk," Dr. Tucker said.
Thus, she noted, a subset of patients can be identified who could benefit from 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 melanoma that once we get people with this inherited predisposition out of the sun, their risk of developing melanoma drops substantially after five years."
