Incidence of familial melanoma and MLM2 gene

The overall incidence of melanoma is increasing world wide. We investigated whether there has been an increase in familial melanoma by studying age at onset among different birth cohorts in 18 melanoma kindreds linked to a predisposition gene (MLM2) on chromosome 9. The cumulative incidence of melanoma was 21-fold higher (95% CI 5.2-84.6) among subjects born after 1959 than in those born before 1900. The expected age of onset of the group born after 1959 was 24 years earlier (21.0 vs 45.0 years). These data support the notion that phenotypic penetrance of the MLM2 gene is increasing, presumably as a result of the interaction of sunlight exposure and mutation at this locus.