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
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
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
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."