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 Hansson; Mark 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

doi:10.1016/j.jid.2017.07.829

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 journal › Article › peer-review

17 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 language	English
Pages (from-to)	2606-2612
Number of pages	7
Journal	Journal of Investigative Dermatology
Volume	137
Issue number	12
Early online date	19 Aug 2017
DOIs	https://doi.org/10.1016/j.jid.2017.07.829
Publication status	Published - 1 Dec 2017

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http://linkinghub.elsevier.com/retrieve/pii/S0022202X17327598Licence: CC BY-NC-ND

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Taylor, N. J., Mitra, N., Goldstein, A. M., Tucker, M. A., Avril, M., Azizi, E., Bergman, W., Bishop, D. T., Bressac-de Paillerets, B., Bruno, W., Calista, D., Cannon-albright, L. A., Cuellar, F., Cust, A. E., Demenais, F., Elder, D. E., Gerdes, A., Ghiorzo, P., Grazziotin, T. C., ... Kanetsky, P. A. (2017). Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families. Journal of Investigative Dermatology, 137(12), 2606-2612. https://doi.org/10.1016/j.jid.2017.07.829

@article{8e614a2b36ec4c679ca8d0e5c2b0b29c,

title = "Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families",

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 = "Taylor, {Nicholas J.} and Nandita Mitra and Goldstein, {Alisa M.} and Tucker, {Margaret A.} and Marie-fran{\c c}oise Avril 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 Anne-marie Gerdes 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 Leachman, {Sancy A.} and Mann, {Graham J.} and Eduardo Nagore and H{\aa}kan Olsson and Palmer, {Jane M.} and Barbara Peri{\'c} 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.}",

note = "{\textcopyright} 2017 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.",

year = "2017",

month = dec,

day = "1",

doi = "10.1016/j.jid.2017.07.829",

language = "English",

volume = "137",

pages = "2606--2612",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "Elsevier",

number = "12",

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Taylor, NJ, Mitra, N, Goldstein, AM, Tucker, MA, Avril, M, Azizi, E, Bergman, W, Bishop, DT, Bressac-de Paillerets, B, Bruno, W, Calista, D, Cannon-albright, LA, Cuellar, F, Cust, AE, Demenais, F, Elder, DE, Gerdes, A, Ghiorzo, P, Grazziotin, TC, Hansson, J, Harland, M, Hayward, NK, Hocevar, M, Höiom, V, Ingvar, C, Landi, MT, Landman, G, Larre-borges, A, Leachman, SA, Mann, GJ, Nagore, E, Olsson, H, Palmer, JM, Perić, B, Pjanova, D, Pritchard, A, Puig, S, Van Der Stoep, N, Wadt, KAW, Whitaker, L, Yang, XR, Newton Bishop, JA, Gruis, NA & Kanetsky, PA 2017, 'Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families', Journal of Investigative Dermatology, vol. 137, no. 12, pp. 2606-2612. https://doi.org/10.1016/j.jid.2017.07.829

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.

PY - 2017/12/1

Y1 - 2017/12/1

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.

U2 - 10.1016/j.jid.2017.07.829

DO - 10.1016/j.jid.2017.07.829

M3 - Article

SN - 0022-202X

VL - 137

SP - 2606

EP - 2612

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 12

ER -

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

Abstract

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