for the Genes Environment and Melanoma (GEM) Study Group

been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated that the lifetime risk (i.e., pene-trance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58 % in Europe to 91 % in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identifi ed in a population-based study of melanoma. Methods: Probands for the study were incident case patients with either fi rst or subsequent melanoma who were identifi ed in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53 % participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplifi ed by polymerase chain reaction of CDKN2A exons 1 α, 2, and 3 and surrounding regions, 65 mutation carriers were identifi ed. Melanoma histories in fi rst-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin – cohort method. Results: The risk of melanoma in CDKN2A mutation carriers was approximately 14 % (95 % CI = 8 % to 22%) by age 50 years, 24 % (95 % CI = 15 % to 34%) by age 70 years, and 28 % (95 % CI = 18 % to 40%) by age 80 years. Eighteen probands had three or more fi rst-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. Conclusions: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case fam-ilies. The preponderance of familial clustering of melanoma occurs in families without identifi able mutations in CDKN2A