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Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees.
Cancer Epidemiol Biomarkers Prev 2005; 14(10):2384-90CE

Abstract

Germline mutations in CDKN2A gene predispose to melanoma with high but incomplete penetrance. Penetrance of CDKN2A gene was found to be significantly influenced by host factors (nevus phenotypes and sunburn) on one hand and by variants of MC1R gene (RHC variants consistently associated with red hair and fair skin) on the other hand. Our goal was to examine the joint effects of MC1R variants and other potential risk factors [total nevi, dysplastic nevi, pigmentary traits (skin, hair and eye color), skin reactions to sunlight, and degree of sun exposure] on CDKN2A penetrance. Clinical, genetic, and covariate data were recorded in 20 French melanoma-prone families with cosegregating CDKN2A mutations. Analysis of the cotransmission of melanoma and CDKN2A mutations was conducted by likelihood-based methods using the regressive logistic models, which can account for a variation of disease risk with age and can include the aforementioned risk factors as covariates. RHC variants, considered either alone or in the presence of pigmentation and nevus phenotypes, were found to increase significantly CDKN2A penetrance. Multivariate analysis, using a stepwise selection procedure, showed significant effects of two factors on melanoma risk in CDKN2A mutations carriers: RHC variants [odds ratio of hazard function (OR), 2.21; P = 0.03] and dysplastic nevi (OR, 2.93; P < 0.01). Such results may have important consequences to improve the prediction of melanoma risk in families.

Authors+Show Affiliations

Institut National de la Sante et de la Recherche Medicale, Université d'Evry, EMI 0006, Tour Evry 2, 523 Place des Terrasses de l'Agora, 91034 Evry, France. chaudru@evry.inserm.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16214921

Citation

Chaudru, Valérie, et al. "Melanocortin-1 Receptor (MC1R) Gene Variants and Dysplastic Nevi Modify Penetrance of CDKN2A Mutations in French Melanoma-prone Pedigrees." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 14, no. 10, 2005, pp. 2384-90.
Chaudru V, Laud K, Avril MF, et al. Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees. Cancer Epidemiol Biomarkers Prev. 2005;14(10):2384-90.
Chaudru, V., Laud, K., Avril, M. F., Minière, A., Chompret, A., Bressac-de Paillerets, B., & Demenais, F. (2005). Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 14(10), pp. 2384-90.
Chaudru V, et al. Melanocortin-1 Receptor (MC1R) Gene Variants and Dysplastic Nevi Modify Penetrance of CDKN2A Mutations in French Melanoma-prone Pedigrees. Cancer Epidemiol Biomarkers Prev. 2005;14(10):2384-90. PubMed PMID: 16214921.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees. AU - Chaudru,Valérie, AU - Laud,Karine, AU - Avril,Marie-Françoise, AU - Minière,Annie, AU - Chompret,Agnès, AU - Bressac-de Paillerets,Brigitte, AU - Demenais,Florence, PY - 2005/10/11/pubmed PY - 2005/12/31/medline PY - 2005/10/11/entrez SP - 2384 EP - 90 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 14 IS - 10 N2 - Germline mutations in CDKN2A gene predispose to melanoma with high but incomplete penetrance. Penetrance of CDKN2A gene was found to be significantly influenced by host factors (nevus phenotypes and sunburn) on one hand and by variants of MC1R gene (RHC variants consistently associated with red hair and fair skin) on the other hand. Our goal was to examine the joint effects of MC1R variants and other potential risk factors [total nevi, dysplastic nevi, pigmentary traits (skin, hair and eye color), skin reactions to sunlight, and degree of sun exposure] on CDKN2A penetrance. Clinical, genetic, and covariate data were recorded in 20 French melanoma-prone families with cosegregating CDKN2A mutations. Analysis of the cotransmission of melanoma and CDKN2A mutations was conducted by likelihood-based methods using the regressive logistic models, which can account for a variation of disease risk with age and can include the aforementioned risk factors as covariates. RHC variants, considered either alone or in the presence of pigmentation and nevus phenotypes, were found to increase significantly CDKN2A penetrance. Multivariate analysis, using a stepwise selection procedure, showed significant effects of two factors on melanoma risk in CDKN2A mutations carriers: RHC variants [odds ratio of hazard function (OR), 2.21; P = 0.03] and dysplastic nevi (OR, 2.93; P < 0.01). Such results may have important consequences to improve the prediction of melanoma risk in families. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/16214921/Melanocortin_1_receptor__MC1R__gene_variants_and_dysplastic_nevi_modify_penetrance_of_CDKN2A_mutations_in_French_melanoma_prone_pedigrees_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=16214921 DB - PRIME DP - Unbound Medicine ER -