How common is the atypical mole syndrome phenotype in apparently sporadic melanoma?

Although patients from some families with the atypical mole syndrome (AMS) are predisposed to melanoma, it is not known how frequently this underlies the apparently sporadic presentation of melanoma.

This study was designed to estimate the frequency of the AMS (dysplastic nevus or FAMMM syndrome) phenotype in a population-based study of patients with melanoma in the United Kingdom and to determine the prevalence of the phenotype in the relatives of the patients with AMS.

The nevi of patients with melanoma and controls in a case-control study, and the nevi of some relatives of patients with AMS, were examined. An AMS scoring system was used to define the AMS phenotype. The familiarity of the AMS phenotype was then determined by screening first-degree relatives of persons with the AMS phenotype.

Forty of 266 (15%) of patients with melanoma had the AMS phenotype compared with 7 of 305 (2%) of the controls (odds ratio 7.5, 95% confidence interval 3.4-16.8). Screening of relatives of patients with melanoma who had the AMS phenotype identified the same phenotype within the families, providing evidence that the AMS phenotype in patients with melanoma is predictive of the same phenotype in relatives, consistent with so-called type D1 AMS.

The AMS phenotype is a potent risk factor for cutaneous melanoma and is present in 15% of patients. Melanoma in the United Kingdom is more common in women than in men, but the AMS phenotype was more frequent in men in this study. It is our hypothesis that the effects of the putative AMS gene are diluted by environmental factors in U.K. women. Screening of relatives of patients with melanoma who have the AMS phenotype may identify persons at increased risk of melanoma.