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

被引：16

作者：

Taylor, Nicholas J. ^{[1
]}

Mitra, Nandita ^{[2
]}

Goldstein, Alisa M. ^{[3
]}

Tucker, Margaret A. ^{[3
]}

Avil, Marie-Francoise ^{[4
,5
]}

Azizi, Esther ^{[6
]}

Bergman, Wilma ^{[7
]}

Bishop, D. Timothy ^{[8
]}

Bressac-de Paillerets, Brigitte ^{[9
]}

Bruno, William ^{[10
,11
]}

Calista, Donato ^{[12
]}

Cannon-Albright, Lisa A. ^{[13
,14
]}

Cuellar, Francisco ^{[15
,16
]}

Cust, Anne E. ^{[17
,18
]}

Demenais, Florence ^{[19
]}

Elder, David E. ^{[20
]}

Gerdes, Anne-Marie ^{[21
]}

Ghiorzo, Paola ^{[8
]}

Grazziotin, Thais C. ^{[22
]}

Hansson, Johan ^{[23
]}

Harland, Mark

Hayward, Nicholas K.

Hocevar, Marko ^{[25
]}

Hoiom, Veronica

Ingvar, Christian ^{[26
,27
]}

Landi, Maria Teresa

Landman, Gilles ^{[28
]}

Larre-Borges, Alejandra ^{[29
]}

Leachman, Sancy A. ^{[30
]}

Mann, Graham J. ^{[31
]}

Nagore, Eduardo ^{[32
]}

Olsson, Hakan

Palmer, Jane M. ^{[24
]}

Peric, Barbara ^{[25
]}

Pjanova, Dace ^{[33
]}

Pritchard, Antonia

Puig, Susana ^{[15
,16
]}

van der Stoep, Nienke ^{[7
]}

Wadt, Karin A. W. ^{[21
]}

Whitaker, Linda ^{[8
]}

Yang, Xiaohong R. ^{[3
]}

Bishop, Julia A. Newton ^{[8
]}

Gruis, Nelleke A. ^{[7
]}

Kanetsky, Peter A. ^{[34
]}

机构：

[1] Texas A&M Hlth Sci Ctr, Dept Epidemiol & Biostat, College Stn, TX USA

[2] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA USA

[3] Natl Canc Inst, Div Canc Epidemiol & Genet, Human Genet Program, Bethesda, MD USA

[4] Hop Cochin, AP HP, Paris, France

[5] Univ Paris 05, Paris, France

[6] Tel Aviv Univ, Sackler Fac Med, Sheba Med Ctr, Dept Dermatol, Tel Aviv, Israel

[7] Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands

[8] St James Univ Hosp, Canc Res UK Clin Ctr Leeds, Leeds Inst Canc & Pathol, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England

[9] Univ Paris Saclay, Gustave Roussy, Dept Biol & Pathol Med, INSERM,U1186, Villejuif, France

[10] Univ Genoa, Dept Internal Med & Med Specialties, Genoa, Italy

[11] IRCCS, AOU San Martino IST, Genoa, Italy

[12] Maurizio Bufalini Hosp, Dermatol Unit, Cesena, Italy

[13] Univ Utah, Dept Genet Epidemiol, Salt Lake City, UT USA

[14] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA

[15] Hosp Clin Barcelona, IDIBAPS, Dermatol Dept, Melanoma Unit, Barcelona, Spain

[16] CIBER Enfermedades Raras, Barcelona, Spain

[17] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW, Australia

[18] Melanoma Inst Australia, Westmead, NSW, Australia

[19] Univ Paris Diderot, Univ Sorbonne Paris Cite, INSERM, Genet Variat & Human Dis Unit,UMR 946, Paris, France

[20] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA USA

[21] Univ Copenhagen Hosp, Dept Clin Genet, Copenhagen, Denmark

[22] Univ Fed Ciencias Sau Porto Alegre, Porto Alegre, RS, Brazil

[23] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden

[24] QIMR Berghofer Med Res Inst, Herston, Qld, Australia

[25] Inst Oncol Ljubljana, Ljubljana, Slovenia

[26] Lund Univ, Dept Clin Sci, Lund, Sweden

[27] Lund Univ, Dept Surg, Lund, Sweden

[28] Univ Fed Sao Paulo, Escola Paulista Med, Dept Pathol, Sao Paulo, Brazil

[29] Univ Republica, Hosp Clin, Unidad Lesiones Pigmentadas Catedra Dermatol, Montevideo, Uruguay

[30] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA

[31] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Sydney, NSW, Australia

[32] Inst Valenciano Oncol, Dept Dermatol, Valencia, Spain

[33] Latvian Biomed Res & Study Ctr, Riga, Latvia

[34] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2017年 / 137卷 / 12期

基金：

英国医学研究理事会; 美国国家卫生研究院; 巴西圣保罗研究基金会; 欧洲研究理事会; 欧盟第七框架计划; 澳大利亚国家健康与医学研究理事会;

关键词：

PANCREATIC-CARCINOMA SYNDROME; GENOME-WIDE ASSOCIATION; MANAGEMENT GENETICS; PRONE FAMILIES; ATYPICAL NEVI; MUTATIONS; LINKAGE; DENSITY; PENETRANCE; CONSORTIUM;

D O I：

10.1016/j.jid.2017.07.829

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

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.

引用

页码：2606 / 2612

页数：7

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