Familial melanoma: Clinical factors associated with germline CDKN2A mutations according to the number of patients affected by melanoma in a family - 14/11/12
, Valérie Chaudru, PhD a, d, e, Hamida Mohamdi, MS a, e, f, Christophe Blondel, MS g, Patricia Margaritte-Jeannin, MS a, e, f, Sébastien Forget, MS g, Eve Corda, MS a, e, Françoise Boitier, MD h, Stéphane Dalle, MD, PhD i, Pierre Vabres, MD, PhD j, Jean-Luc Perrot, MD k, Dominique Stoppa Lyonnet, MD, PhD l, m, Hélène Zattara, MD n, Sandrine Mansard, MD o, Florent Grange, MD, PhD p, Marie-Thérèse Leccia, MD, PhD q, Lynda Vincent-Fetita, MD h, Ludovic Martin, MD, PhD r, Béatrice Crickx, MD, PhD b, c, Pascal Joly, MD, PhD s, Luc Thomas, MD, PhD i, French Familial Melanoma Study Groupt
Brigitte Bressac-de Paillerets, PharmD, PhD a, g, Marie-Françoise Avril, MD, PhD h, m, Florence Demenais, MD a, e, f
Reprint requests: Eve Maubec, MD, INSERM, U946, Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain, 27 Rue Juliette Dodu, 75010 Paris, France.Abstract |
Background |
Features associated with an increased frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations have been identified in families with 3 or more patients with cutaneous melanoma (CM). However, in families with 2 patients with CM, which represent the majority of familial melanoma, these factors have been rarely studied.
Objective |
We investigated association of 3 clinical features with the presence of a CDKN2A mutation in a family by extent of CM family clustering (2 vs ≥3 patients with CM among first-degree relatives in a family).
Methods |
We included 483 French families that comprised 387 families with 2 patients with CM (F2 families) and 96 families with 3 or more patients with CM (F3+ families). Three clinical factors were examined individually and in a joint analysis: median age at diagnosis younger than 50 years, and 1 or more patient in a family with multiple primary melanoma or with pancreatic cancer.
Results |
The frequency of CDKN2A mutations was higher in F3+ families (32%) than in F2 families (13%). Although early age at melanoma diagnosis and occurrence of multiple primary melanoma in 1 or more patient were significantly associated with the risk of a CDKN2A mutation in F2 families, early age at melanoma diagnosis and occurrence of pancreatic cancer in a family were significantly associated with CDKN2A mutations in F3+ families.
Limitations |
The study was not population based.
Conclusions |
This study shows that factors associated with CDKN2A mutations differ by extent of CM family clustering. It indicates that, in France, families with 2 patients with CM are eligible for genetic testing especially when there is an early age at CM diagnosis and/or 1 or more patients with multiple primary melanoma.
Le texte complet de cet article est disponible en PDF.Key words : cutaneous melanoma, cyclin-dependent kinase inhibitor 2A mutations, family clustering, genetic testing, multiple primary melanomas, pancreatic cancer
Abbreviations used : ARF, CDKN2A, CI, CM, F2 families, F3+ families, MPM, OR, PC
Plan
| Supported by Institut National de la Santé et de la Recherche Médicale (including an INSERM Research Fellowship for hospital-based scientists to Dr Bressac-de Paillerets), Université Paris Diderot, and the National Institutes of Health RO1 CA-83115 (Dr Demenais); Programme Hospitalier de Recherche Clinique, PHRC 2007-AOM-07-195 (Drs Demenais and Avril); and Institut National du Cancer. |
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| French melanoma oncogenetic network coordinated by Dr Bressac-de Paillerets and Institut National du Cancer (French melanoma oncogenetic network coordinated by Dr Bressac-de Paillerets). |
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| Drs Maubec, Chaudru, Bressac-de Paillerets, Avril, and Demenais contributed equally to this article. |
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| Conflicts of interest: None declared. |
Vol 67 - N° 6
P. 1257 - décembre 2012 Retour au numéro
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