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CDKN2A mutations have a modest impact on the incidence of melanoma
People who carry a mutation in the melanoma susceptibility gene CDKN2A have a much lower risk of melanoma than has been suggested by previous estimates, although this risk is higher than that in the general population.
In addition, most familial clusters of melanoma occur in families without identifiable mutations in this gene.
. Malignant melanoma frequently clusters in families. Studies of hereditary melanoma families have estimated that carriers of CDKN2A mutations have a high lifetime risk ranging from 58% to 91% of developing melanoma by age 80. The lifetime risk in the general population is just 2%.
To obtain risk estimates that may be more representative of gene mutation carrier risks in the general population, Colin B. Begg, of Memorial Sloan-Kettering Cancer Center in New York, and colleagues evaluated 3,550 melanoma patients for CDKN2A mutations, finding mutations in 65 patients. The melanoma histories of the first-degree relatives of these patients were used to calculate the lifetime risk of melanoma in CDKN2A mutation carriers.
The risk of melanoma in CDKN2A mutation carriers was estimated to be 14% by age 50, 24% by age 70, and 28% by age 80. Of the 18 melanoma patients who had three or more first-degree relatives with melanoma, one only was a CDKN2A mutation carrier.
" Our study suggests that CDKN2A mutations have a modest impact on the incidence of melanoma on a population basis and that genetic testing of families with a history of melanoma would be likely to identify relatively few with mutations in CDKN2A," the authors write.
In an editorial, Alisa M. Goldstein, and Margaret A. Tucker, of the National Cancer Institute, agree that it would be premature to consider widespread testing for this genetic mutation. They estimate that, based on the results of Begg and colleagues, testing all 59,580 patients newly diagnosed with melanoma in the United States in 2005 would yield only 779 mutation carriers, of which 36% would have neither a family nor personal history of melanoma. "Although CDKN2A mutation status is an important component of familial melanoma susceptibility," they write, "it is not the only risk factor that should be considered in counseling patients or their family members."
Source: Journal of the National Cancer Institute, 2005
