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

GenoMEL Study Group

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 = 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 (US)
Pages (from-to)2606-2612
Number of pages7
JournalJournal of Investigative Dermatology
Volume137
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Nevus
Melanoma
Blood
Genes
Phenotype
Odds Ratio
Confidence Intervals
Mutation
Germ-Line Mutation
Carcinogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families. / GenoMEL Study Group.

In: Journal of Investigative Dermatology, Vol. 137, No. 12, 01.12.2017, p. 2606-2612.

Research output: Contribution to journalArticle

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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 = 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.",
author = "{GenoMEL Study Group} and Taylor, {Nicholas J.} and Nandita Mitra and Goldstein, {Alisa M.} and Tucker, {Margaret A.} and Avril, {Marie Fran{\cc}oise} and Esther Azizi and Wilma Bergman and Bishop, {D. Timothy} and {Bressac-de Paillerets}, Brigitte and William Bruno and Donato Calista and Cannon-Albright, {Lisa A.} and Francisco Cuellar and Cust, {Anne E.} and Florence Demenais and Elder, {David E.} and Gerdes, {Anne Marie} and Paola Ghiorzo and Grazziotin, {Thais C.} and Johan Hansson and Mark Harland and Hayward, {Nicholas K.} and Marko Hocevar and Veronica H{\"o}iom and Christian Ingvar and Landi, {Maria Teresa} and Gilles Landman and Alejandra Larre-Borges and Sancy Leachman and Mann, {Graham J.} and Eduardo Nagore and H{\aa}kan Olsson and Palmer, {Jane M.} and Barbara Perić and Dace Pjanova and Antonia Pritchard and Susana Puig and {van der Stoep}, Nienke and Wadt, {Karin A.W.} and Linda Whitaker and Yang, {Xiaohong R.} and {Newton Bishop}, {Julia A.} and Gruis, {Nelleke A.} and Kanetsky, {Peter A.}",
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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.

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