title: Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma families.
abstract: OBJECTIVE
  We report the largest study to date analyzing the risk of cancers other than melanoma in melanoma families positive for the same CDKN2A mutation.
  
  
  METHODS
  We studied family members of 22 families positive for the p16-Leiden founder mutation who had attended a surveillance clinic or were their close relatives. Within this cohort, observed and expected rates of cancer were computed by mutation status consisting of 221 (proven plus obligate) carriers, 639 (proven plus obligate) noncarriers, and 668 first-degree relatives whose carrier risk was estimated from the relationship to known carriers and the age and melanoma status of that person and their relatives.
  
  
  RESULTS
  Our analysis shows a relative risk (RR) of cancer other than melanoma and nonmelanoma skin cancer of 4.4 [95% confidence interval (95% CI), 3.3-5.6], predominantly attributable to the increased risk for pancreatic cancer (RR, 46.6; 95% CI, 24.7-76.4), but also for other cancers. We provide substantial proof for pancreatic cancer being a key component of the p16-Leiden phenotype. Inclusion of this cancer in a penetrance analysis leads to an estimated RR of pancreatic cancer for mutation carriers of 47.8 (95% CI, 28.4-74.7).
  
  
  CONCLUSIONS
  This study shows clear evidence of increased risk of cancers other than melanoma in CDKN2A families carrying the p16-Leiden mutation. Further research is necessary to determine if similar risks apply to families with CDKN2A mutations other than p16-Leiden.
authors.affiliation: Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Femke A
authors.initials: FA
authors.lastname: de Snoo
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Wilma
authors.initials: W
authors.lastname: Bergman
authors.forename: Inge
authors.initials: I
authors.lastname: van Leeuwen
authors.forename: Clasine
authors.initials: C
authors.lastname: van der Drift
authors.forename: Frans A
authors.initials: FA
authors.lastname: van Nieuwpoort
authors.forename: Coby J
authors.initials: CJ
authors.lastname: Out-Luiting
authors.forename: Hans F
authors.initials: HF
authors.lastname: Vasen
authors.forename: Jeanet A C
authors.initials: JA
authors.lastname: ter Huurne
authors.forename: Rune R
authors.initials: RR
authors.lastname: Frants
authors.forename: Rein
authors.initials: R
authors.lastname: Willemze
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.forename: Nelleke A
authors.initials: NA
authors.lastname: Gruis
mesh_terms: D005260:Female; D018703:Founder Effect; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D009377:Multiple Endocrine Neoplasia / Q000453:epidemiology*; D009154:Mutation; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000235:genetics*