Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents

Research output: Contribution to journalArticle


BACKGROUND: The major factors individually reported to be associated with an increased frequency of CDKN2A mutations are increased number of patients with melanoma in a family, early age at melanoma diagnosis, and family members with multiple primary melanomas (MPM) or pancreatic cancer. METHODS: These four features were examined in 385 families with > or =3 patients with melanoma pooled by 17 GenoMEL groups, and these attributes were compared across continents. RESULTS: Overall, 39% of families had CDKN2A mutations ranging from 20% (32/162) in Australia to 45% (29/65) in North America to 57% (89/157) in Europe. All four features in each group, except pancreatic cancer in Australia (p = 0.38), individually showed significant associations with CDKN2A mutations, but the effects varied widely across continents. Multivariate examination also showed different predictors of mutation risk across continents. In Australian families, > or =2 patients with MPM, median age at melanoma diagnosis < or =40 years and > or =6 patients with melanoma in a family jointly predicted the mutation risk. In European families, all four factors concurrently predicted the risk, but with less stringent criteria than in Australia. In North American families, only > or =1 patient with MPM and age at diagnosis < or =40 years simultaneously predicted the mutation risk. CONCLUSIONS: The variation in CDKN2A mutations for the four features across continents is consistent with the lower melanoma incidence rates in Europe and higher rates of sporadic melanoma in Australia. The lack of a pancreatic cancer-CDKN2A mutation relationship in Australia probably reflects the divergent spectrum of mutations in families from Australia versus those from North America and Europe. GenoMEL is exploring candidate host, genetic and/or environmental risk factors to better understand the variation observed.


  • Alisa M Goldstein
  • May Chan
  • Mark Harland
  • Nicholas K Hayward
  • Florence Demenais
  • D Timothy Bishop
  • Esther Azizi
  • Wilma Bergman
  • Giovanna Bianchi-Scarra
  • William Bruno
  • Donato Calista
  • Lisa A Cannon Albright
  • Valerie Chaudru
  • Agnes Chompret
  • Francisco Cuellar
  • David E Elder
  • Paola Ghiorzo
  • Elizabeth M Gillanders
  • Nelleke A Gruis
  • Johan Hansson
  • And 20 others
  • David Hogg
  • Elizabeth A Holland
  • Peter A Kanetsky
  • Richard F Kefford
  • Maria Teresa Landi
  • Julie Lang
  • Sancy A Leachman
  • Rona M MacKie
  • Veronica Magnusson
  • Graham J Mann
  • Julia Newton Bishop
  • Jane M Palmer
  • Susana Puig
  • Joan A Puig-Butille
  • Mitchell Stark
  • Hensin Tsao
  • Margaret A Tucker
  • Linda Whitaker
  • Emanuel Yakobson
  • The Lund Melanoma Study Group23 and the Melanoma Genetics Consortium (GenoMEL)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics


  • multiple primary melanomas, melanoma, CDKN2A, pancreatic cancer
Original languageEnglish
Pages (from-to)99-106
JournalJournal of Medical Genetics
Issue number2
Publication statusPublished - 2007
Publication categoryResearch