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

Goldstein, Alisa M; Chan, May; Harland, Mark; Hayward, Nicholas K; Demenais, Florence; Bishop, D Timothy; Azizi, Esther; Bergman, Wilma; Bianchi-Scarra, Giovanna and Bruno, William, et al. (2007) In Journal of Medical Genetics 44(2). p.99-106
Abstract
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... (More)
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. (Less)
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publication status
published
subject
keywords
multiple primary melanomas, melanoma, CDKN2A, pancreatic cancer
in
Journal of Medical Genetics
volume
44
issue
2
pages
99 - 106
publisher
BMJ Publishing Group
external identifiers
  • pmid:16905682
  • scopus:33847282821
ISSN
0022-2593
DOI
10.1136/jmg.2006.043802
language
English
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yes
id
80a9f5a8-c439-419a-805f-2d7e9d7a0e08 (old id 1138582)
date added to LUP
2008-08-19 13:04:23
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2017-11-19 04:13:42
@article{80a9f5a8-c439-419a-805f-2d7e9d7a0e08,
  abstract     = {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 &gt; 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, &gt; or =2 patients with MPM, median age at melanoma diagnosis &lt; or =40 years and &gt; 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 &gt; or =1 patient with MPM and age at diagnosis &lt; 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.},
  author       = {Goldstein, Alisa M and Chan, May and Harland, Mark and Hayward, Nicholas K and Demenais, Florence and Bishop, D Timothy and Azizi, Esther and Bergman, Wilma and Bianchi-Scarra, Giovanna and Bruno, William and Calista, Donato and Albright, Lisa A Cannon and Chaudru, Valerie and Chompret, Agnes and Cuellar, Francisco and Elder, David E and Ghiorzo, Paola and Gillanders, Elizabeth M and Gruis, Nelleke A and Hansson, Johan and Hogg, David and Holland, Elizabeth A and Kanetsky, Peter A and Kefford, Richard F and Landi, Maria Teresa and Lang, Julie and Leachman, Sancy A and MacKie, Rona M and Magnusson, Veronica and Mann, Graham J and Newton Bishop, Julia and Palmer, Jane M and Puig, Susana and Puig-Butille, Joan A and Stark, Mitchell and Tsao, Hensin and Tucker, Margaret A and Whitaker, Linda and Yakobson, Emanuel and Lund Melanoma Study Group23 and the Melanoma Genetics Consortium (GenoMEL), The},
  issn         = {0022-2593},
  keyword      = {multiple primary melanomas,melanoma,CDKN2A,pancreatic cancer},
  language     = {eng},
  number       = {2},
  pages        = {99--106},
  publisher    = {BMJ Publishing Group},
  series       = {Journal of Medical Genetics},
  title        = {Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents},
  url          = {http://dx.doi.org/10.1136/jmg.2006.043802},
  volume       = {44},
  year         = {2007},
}