EXCESS CANCER MORTALITY IN 6 DUTCH PEDIGREES WITH THE FAMILIAL ATYPICAL MULTIPLE MOLE-MELANOMA SYNDROME FROM 1830 TO 1994

An increased incidence of systemic cancers has been described in some reports of familial atypical multiple mole-melanoma kindreds, If the g ene defect underlying the familial atypical multiple mole-melanoma syn drome is not only important for the development of melanoma of the ski n, the impact of the defect on life expectancy may be much higher than previously thought. We investigated all-cause mortality from 1830 to the present and causes of death from 1941 to 1994 in proven, obligate, and potential CDKN2 mutation carriers to obtain an estimate of the im pact of a hereditary defect of the CDKN2 gene on mortality. From 1830 to 1994 there were 65 deaths, although only 42 deaths were expected [s tandardized mortality ratio (SMR) 1.6, 95% confidence interval (CI) 1. 2-2.0] and the SMR doubled with calendar time, Excess mortality was sh own in most of the families, but was confined to ages 35-70 y (SMR 2.1 , 95%CI 1.5-2.9). Excess mortality could be fully attributed to cancer mortality, especially to pancreatic carcinoma and melanoma of the ski n, There appeared to be some heterogeneity among the families, especia lly due to the specific cancer pattern within a family. The impact of the defect of the CDKN2 gene is rising over calendar time, mainly beca use the mortality in the general population has been falling. Excess m ortality was not only due to melanoma, but also to pancreatic carcinom a. Therefore, follow-up programs of affected family members should not be confined to a regular check of the atypical nevi.