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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 and Bruno, William, et al. (2017) In Journal of Investigative Dermatology 137(12). p.2606-2612
Abstract

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 =... (More)

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.

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Journal of Investigative Dermatology
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137
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12
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7 pages
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Nature Publishing Group
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  • scopus:85035010048
  • wos:000415797600026
ISSN
0022-202X
DOI
10.1016/j.jid.2017.07.829
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English
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yes
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71e33702-a958-487a-a5bb-20e967110f73
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2017-12-12 08:58:17
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2018-01-16 13:27:37
@article{71e33702-a958-487a-a5bb-20e967110f73,
  abstract     = {<p>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.</p>},
  author       = {Taylor, Nicholas J. and Mitra, Nandita and Goldstein, Alisa M. and Tucker, Margaret A. and Avril, Marie Françoise and Azizi, Esther and Bergman, Wilma and Bishop, D. Timothy and Bressac-de Paillerets, Brigitte and Bruno, William and Calista, Donato and Cannon-Albright, Lisa A. and Cuellar, Francisco and Cust, Anne E. and Demenais, Florence and Elder, David E. and Gerdes, Anne Marie and Ghiorzo, Paola and Grazziotin, Thais C. and Hansson, Johan and Harland, Mark and Hayward, Nicholas K. and Hocevar, Marko and Höiom, Veronica and Ingvar, Christian and Landi, Maria Teresa and Landman, Gilles and Larre-Borges, Alejandra and Leachman, Sancy A. and Mann, Graham J. and Nagore, Eduardo and Olsson, Håkan and Palmer, Jane M. and Perić, Barbara and Pjanova, Dace and Pritchard, Antonia and Puig, Susana and van der Stoep, Nienke and Wadt, Karin A.W. and Whitaker, Linda and Yang, Xiaohong R. and Newton Bishop, Julia A. and Gruis, Nelleke A. and Kanetsky, Peter A. and , },
  issn         = {0022-202X},
  language     = {eng},
  month        = {12},
  number       = {12},
  pages        = {2606--2612},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Investigative Dermatology},
  title        = {Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families},
  url          = {http://dx.doi.org/10.1016/j.jid.2017.07.829},
  volume       = {137},
  year         = {2017},
}