Author/Editor		Taylor, Nicholas J.; Mitra, Nandita; Goldstein, Alisa M.; Tucker, Margaret A.; Avril, Marie-Françoise; Azizi, Esther; Bergman, Wilma; Bishop, David Timothy; Hočevar, Marko; Perić, Barbara
Title		Germline variation at CDKN2A and associations with nevus phenotypes among members of melanoma families
Type		članek
Vol. and No.		Letnik 137, št. 12
Publication year		2017
Volume		str. 2606-2612
ISSN		0022-202X - The Journal of investigative dermatology
Language		eng
Abstract		Germline mutations in the cyclin-dependent kinase inhibitor 2A gene (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 to individuals without a pathogenic mutation, those who carried one had an overall higher prevalence of atypical (OR=1.64; 95% CI: 1.18, 2.28) nevi, but not 2 mm nevi (OR=1.06; 95% CI: 0.92, 1.21) or 5 mm nevi (OR=1.26; 95% CI: 0.94, 1.70). Stratification by case status revealed more pronounced positive associations among non-case family members, who were nearly three times (OR=2.91; 95% CI: 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 are supportive of the hypothesis that unidentified nevogenic genes are co-inherited with CDKN2A and may influence carcinogenesis.
Keywords		melanom genetika mutacije karcinogeneza