Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families. / Taylor, Nicholas J; Mitra, Nandita; Goldstein, Alisa M; Tucker, Margaret A; Avril, Marie-Françoise; Azizi, Esther; Bergman, Wilma; Bishop, D Timothy; Bressac-de Paillerets, Brigitte; Bruno, William; Calista, Donato; Cannon-Albright, Lisa A; Cuellar, Francisco; Cust, Anne E; Demenais, Florence; Elder, David E; Gerdes, Anne-Marie; Ghiorzo, Paola; Grazziotin, Thais C; Hansson, Johan; Harland, Mark; Hayward, Nicholas K; Hocevar, Marko; Höiom, Veronica; Ingvar, Christian; Landi, Maria Teresa; Landman, Gilles; Larre-Borges, Alejandra; Leachman, Sancy A; Mann, Graham J; Nagore, Eduardo; Olsson, Håkan; Palmer, Jane M; Perić, Barbara; Pjanova, Dace; Pritchard, Antonia; Puig, Susana; van der Stoep, Nienke; Wadt, Karin A W; Whitaker, Linda; Yang, Xiaohong R; Newton Bishop, Julia A; Gruis, Nelleke A; Kanetsky, Peter A; GenoMEL Study Group.
I: The Journal of Investigative Dermatology, Bind 137, Nr. 12, 12.2017, s. 2606-2612.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families
AU - Taylor, Nicholas J
AU - Mitra, Nandita
AU - Goldstein, Alisa M
AU - Tucker, Margaret A
AU - Avril, Marie-Françoise
AU - Azizi, Esther
AU - Bergman, Wilma
AU - Bishop, D Timothy
AU - Bressac-de Paillerets, Brigitte
AU - Bruno, William
AU - Calista, Donato
AU - Cannon-Albright, Lisa A
AU - Cuellar, Francisco
AU - Cust, Anne E
AU - Demenais, Florence
AU - Elder, David E
AU - Gerdes, Anne-Marie
AU - Ghiorzo, Paola
AU - Grazziotin, Thais C
AU - Hansson, Johan
AU - Harland, Mark
AU - Hayward, Nicholas K
AU - Hocevar, Marko
AU - Höiom, Veronica
AU - Ingvar, Christian
AU - Landi, Maria Teresa
AU - Landman, Gilles
AU - Larre-Borges, Alejandra
AU - Leachman, Sancy A
AU - Mann, Graham J
AU - Nagore, Eduardo
AU - Olsson, Håkan
AU - Palmer, Jane M
AU - Perić, Barbara
AU - Pjanova, Dace
AU - Pritchard, Antonia
AU - Puig, Susana
AU - van der Stoep, Nienke
AU - Wadt, Karin A W
AU - Whitaker, Linda
AU - Yang, Xiaohong R
AU - Newton Bishop, Julia A
AU - Gruis, Nelleke A
AU - Kanetsky, Peter A
AU - GenoMEL Study Group
N1 - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
KW - Cyclin-Dependent Kinase Inhibitor p18/genetics
KW - DNA Mutational Analysis
KW - Family Health
KW - Female
KW - Genotype
KW - Germ-Line Mutation
KW - Humans
KW - Male
KW - Melanoma/genetics
KW - Nevus/genetics
KW - Nevus, Pigmented/genetics
KW - Odds Ratio
KW - Phenotype
KW - Registries
KW - Skin Neoplasms/genetics
U2 - 10.1016/j.jid.2017.07.829
DO - 10.1016/j.jid.2017.07.829
M3 - Journal article
C2 - 28830827
VL - 137
SP - 2606
EP - 2612
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 12
ER -
ID: 196908249