AGE AT DIAGNOSIS AND TRANSMISSION OF INVASIVE MELANOMA IN 23 FAMILIESWITH CUTANEOUS MALIGNANT-MELANOMA DYSPLASTIC NEVI

Background: Familial melanoma patients tend to have an earlier age at first melanoma diagnosis, thinner lesions, a different histologic dist ribution, and a higher frequency of multiple primary melanomas than pa tients with nonfamilial melanoma. Previous examination of a large mela noma kindred from Texas suggested that although cutaneous malignant me lanoma (CMM) was transmitted in an autosomal dominant fashion, there w ere sex differences in penetrance and disease expression. Purpose: Thi s study further evaluated the age at diagnosis, sex difference in pene trance and disease expression, and segregation of familial CMM. Method s: We evaluated the age at diagnosis and transmission of CMM in 23 U.S . white families with CMM/dysplastic nevi who had been followed 5-17 y ears. We estimated the median and mean ages at diagnosis of invasive m elanoma for all individuals, for men and women separately, and by gene ration. Using the computer program BMDP1L, we also estimated the cumul ative probability of an offspring developing CMM as a function of age according to whether the mother or father had melanoma. In addition, w e used a life-table approach to estimate the probability that offsprin g of CMM parents were affected with CMM (penetrance). Results: The med ian age at diagnosis in the 23 kindreds (n = 106) was 33 years, substa ntially less than that of patients with sporadic melanomas in the U.S. white population. For females, the median age at diagnosis was 29 yea rs; for males, it was 36 years. Nine percent of the case patients deve loped CMM before age 20 compared with 2% in the general population. Th ere was little difference in the transmission pattern of melanoma betw een males and females in the 23 families, although sons of CMM parents had a higher risk of CMM than daughters of CMM parents. This differen ce was, however, based on small numbers and was not statistically sign ificant. The penetrance estimates for CMM were high. They rose rapidly from 6% at age 18 to 85% by age 48. The median age at diagnosis of in vasive melanoma decreased dramatically in successive generations; the reduction was 11-16 years per generation and was statistically signifi cant (P<.0001). Conclusions and Implications: Although this reduction in median age at diagnosis may result partly from increased surveillan ce in hereditary melanoma families and the fact that individuals in th e younger generations have not yet reached the highest at-risk ages fo r developing melanoma, the possibility of changes in melanoma risk and risk factors, genetic and/or environmental, across generations should be considered.