Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families

Nicholas J. Taylor, Nandita Mitra, Alisa M. Goldstein, Margaret A. Tucker, Marie-françoise Avril, Esther Azizi, Wilma Bergman, D. Timothy Bishop, Brigitte Bressac-de Paillerets, William Bruno, Donato Calista, Lisa A. Cannon-albright, Francisco Cuellar, Anne E. Cust, Florence Demenais, David E. Elder, Anne-marie Gerdes, Paola Ghiorzo, Thais C. Grazziotin, Johan HanssonMark Harland, Nicholas K. Hayward, Marko Hocevar, Veronica Höiom, Christian Ingvar, Maria Teresa Landi, Gilles Landman, Alejandra Larre-borges, Sancy A. Leachman, Graham J. Mann, Eduardo Nagore, Håkan Olsson, Jane M. Palmer, Barbara Perić, Dace Pjanova, Antonia Pritchard, Susana Puig, Nienke Van Der Stoep, Karin A.w. Wadt, Linda Whitaker, Xiaohong R. Yang, Julia A. Newton Bishop, Nelleke A. Gruis, Peter A. Kanetsky

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Germline mutations in CDKN2A are frequently identified among melanoma kindreds and are associated with increased atypical nevus counts. However, a clear relationship between pathogenic CDKN2A mutation carriage and other nevus phenotypes including counts of common acquired nevi has not yet been established. Using data from GenoMEL, we investigated the relationships between CDKN2A mutation carriage and 2-mm, 5-mm, and atypical nevus counts among blood-related members of melanoma families. Compared with individuals without a pathogenic mutation, those who carried one had an overall higher prevalence of atypical (odds ratio = 1.64; 95% confidence interval = 1.18–2.28) nevi but not 2-mm nevi (odds ratio = 1.06; 95% confidence interval = 0.92–1.21) or 5-mm nevi (odds ratio = 1.26; 95% confidence interval = 0.94–1.70). Stratification by case status showed more pronounced positive associations among non-case family members, who were nearly three times (odds ratio = 2.91; 95% confidence interval = 1.75–4.82) as likely to exhibit nevus counts at or above the median in all three nevus categories simultaneously when harboring a pathogenic mutation (vs. not harboring one). Our results support the hypothesis that unidentified nevogenic genes are co-inherited with CDKN2A and may influence carcinogenesis.
Original languageEnglish
Pages (from-to)2606-2612
Number of pages7
JournalJournal of Investigative Dermatology
Issue number12
Early online date19 Aug 2017
Publication statusPublished - 1 Dec 2017


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