The overall incidence of melanoma is increasing world wide. We investi
gated whether there has been an increase in familial melanoma by study
ing age at onset among different birth cohorts in 18 melanoma kindreds
linked to a predisposition gene (MLM2) on chromosome 9. The cumulativ
e incidence of melanoma was 21-fold higher (95% CI 5.2-84.6) among sub
jects 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 4
5.0 years). These data support the notion that phenotypic penetrance o
f the MLM2 gene is increasing, presumably as a result of the interacti
on of sunlight exposure and mutation at this locus.