title: Familial melanoma: clinical factors associated with germline CDKN2A mutations according to the number of patients affected by melanoma in a family.
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.
  
  
  CONCLUSIONS
  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.
authors: INSERM (Institut National de Santé et de Recherche Médicale), Genetic Variation and Human Diseases Unit (U946), Paris, France. eve.maubec@bch.aphp.fr
authors: Eve
authors: E
authors: Maubec
authors: Valérie
authors: V
authors: Chaudru
authors: Hamida
authors: H
authors: Mohamdi
authors: Christophe
authors: C
authors: Blondel
authors: Patricia
authors: P
authors: Margaritte-Jeannin
authors: Sébastien
authors: S
authors: Forget
authors: Eve
authors: E
authors: Corda
authors: Françoise
authors: F
authors: Boitier
authors: Stéphane
authors: S
authors: Dalle
authors: Pierre
authors: P
authors: Vabres
authors: Jean-Luc
authors: JL
authors: Perrot
authors: Dominique Stoppa
authors: DS
authors: Lyonnet
authors: Hélène
authors: H
authors: Zattara
authors: Sandrine
authors: S
authors: Mansard
authors: Florent
authors: F
authors: Grange
authors: Marie-Thérèse
authors: MT
authors: Leccia
authors: Lynda
authors: L
authors: Vincent-Fetita
authors: Ludovic
authors: L
authors: Martin
authors: Béatrice
authors: B
authors: Crickx
authors: Pascal
authors: P
authors: Joly
authors: Luc
authors: L
authors: Thomas
authors: Brigitte
authors: B
authors: Bressac-de Paillerets
authors: Marie-Françoise
authors: MF
authors: Avril
authors: Florence
authors: F
authors: Demenais
mesh_terms: D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D008545:Melanoma / Q000453:epidemiology* / Q000235:genetics*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16