Dysplastic nevi as a melanoma risk factor in patients with familial melanoma.

BACKGROUND: Familial melanoma has been associated with "clinically atypical moles" or "dysplastic nevi," (DN) which are markers for increased melanoma risk. In addition, melanomas in these kindreds present at a younger age, and tend to be multiple. METHODS: Melanoma incidence rates were determined for 710 members of 311 melanoma families, defined as kindreds in which melanoma had occurred in two or more blood relatives. Patients were classified either clinically or histologically as expressing DN. Melanomas that occurred before the first examination were recorded, and patients were followed prospectively for new melanomas. RESULTS: In prospective follow-up, the age-adjusted melanoma incidence rate was 1710/100,000 patient-years in family members with DN. In contrast, the rate was zero (no melanomas occurred) in family members without DN. For family members with DN, but without a history of melanoma, the age-adjusted incidence rate of melanoma was 413/100,000 patient-years, whereas the rate was 2779/100,000 patient-years in family members with DN and a history of melanoma. CONCLUSIONS: Dysplastic nevi and a history of melanoma are strong risk factors for subsequent melanoma. Prognostic factors are greatly improved for patients with melanomas diagnosed in follow-up compared with the first two melanomas in each kindred. These findings warrant surveillance of individuals with DN who are members of familial melanoma kindreds.

Familial cutaneous melanoma and two-mutational-event modeling.

BACKGROUND: According to the Knudson two-mutational-event theory, two mutations at a genetic locus may be required for the development of some cancers. Persons who have inherited a defect in one chromosome and therefore require only one more mutation for cancer development are at a higher risk of manifesting cancer at a younger age than persons without an inherited mutation, who need two acquired "hits." This difference allows one to distinguish familial and sporadic types of the same malignancy by evaluating age of disease onset. METHODS: To study the role of inheritance in the etiology of familial cutaneous melanoma, characteristics of patients with familial versus nonfamilial melanoma were analyzed according to the Knudson two-mutational-event model. RESULTS: The familial versus nonfamilial graphs, based on age of diagnosis, did not support this model. However, there was a statistically significant earlier age of diagnosis for patients with familial melanoma. Melanoma thickness was less (i.e., earlier cancer at possibly younger age) for patients with a positive versus a negative family history. Conversely, linear regression, after adjusting for tumor thickness, showed that patients with hereditary melanoma still manifested earlier ages of diagnosis of melanoma compared with sporadic patients. CONCLUSIONS: Genetic patterns other than the two-step model, additional family-related factors, patient-physician sensitization due to a family history, or a combination of these factors might explain this age difference. More complex multistep modeling of the data may be helpful in better characterizing the genetic patterns of cutaneous melanoma.