Advanced

Germline CDKN2A Mutation Status and Survival in Familial Melanoma Cases

Helgadottir, Hildur; Höiom, Veronica; Tuominen, Rainer; Nielsen, Kari LU ; Jönsson, Göran B LU ; Olsson, Håkan LU and Hansson, Johan (2016) In Journal of the National Cancer Institute 108(11).
Abstract

BACKGROUND: Germline mutations in CDKN2A have been associated with increased risk of melanoma and tobacco-related cancers in respiratory and upper digestive tissues. In CDKN2A wild-type (wt) melanoma families, other known high-risk, melanoma-predisposing mutations are rare, and no increased risk has been observed for nonskin cancers in this group. This study is the first to compare survival in germline CDKN2A mutated (mut) and nonmutated melanoma cases.

METHODS: Melanoma-prone families participating in this study were identified through a nationwide predictive program starting in 1987. Information on cancer diagnoses (types, stages, and dates) and deaths (causes and dates) were obtained through the Swedish Cancer Registry and... (More)

BACKGROUND: Germline mutations in CDKN2A have been associated with increased risk of melanoma and tobacco-related cancers in respiratory and upper digestive tissues. In CDKN2A wild-type (wt) melanoma families, other known high-risk, melanoma-predisposing mutations are rare, and no increased risk has been observed for nonskin cancers in this group. This study is the first to compare survival in germline CDKN2A mutated (mut) and nonmutated melanoma cases.

METHODS: Melanoma-prone families participating in this study were identified through a nationwide predictive program starting in 1987. Information on cancer diagnoses (types, stages, and dates) and deaths (causes and dates) were obtained through the Swedish Cancer Registry and Cause of Death Registry. Kaplan Meier and Cox proportional hazards regression models were used to assess survival in CDKN2A(mut) (n = 96) and CDKN2A(wt) (n = 377) familial melanoma cases and in matched sporadic melanoma cases (n = 1042). All statistical tests were two-sided.

RESULTS: When comparing CDKN2A(mut) and CDKN2A(wt) melanoma cases, after adjusting for age, sex, and T classification, CDKN2A(mut) had worse survival than melanoma (hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.49 to 4.21) and than nonmelanoma cancers (HR = 7.77, 95% CI = 3.65 to 16.51). Compared with matched sporadic cases, CDKN2A(mut) cases had statistically significantly worse survival from both melanoma and nonmelanoma cancers while no differences in survival were seen in CDKN2A(wt) compared with sporadic cases.

CONCLUSIONS: CDKN2A(mut) cases had statistically significantly worse survival than nonmelanoma cancers and, intriguingly, also from melanoma, compared with melanoma cases with no CDKN2A mutations. Further studies are required to elucidate possible mechanisms behind increased carcinogen susceptibility and the more aggressive melanoma phenotype in CDKN2A mutation carriers.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the National Cancer Institute
volume
108
issue
11
publisher
Oxford University Press
ISSN
1460-2105
DOI
10.1093/jnci/djw135
language
English
LU publication?
yes
id
6001dfea-0576-45e1-947e-1f6302af96e8
date added to LUP
2016-09-18 11:30:56
date last changed
2016-11-14 09:43:03
@misc{6001dfea-0576-45e1-947e-1f6302af96e8,
  abstract     = {<p>BACKGROUND: Germline mutations in CDKN2A have been associated with increased risk of melanoma and tobacco-related cancers in respiratory and upper digestive tissues. In CDKN2A wild-type (wt) melanoma families, other known high-risk, melanoma-predisposing mutations are rare, and no increased risk has been observed for nonskin cancers in this group. This study is the first to compare survival in germline CDKN2A mutated (mut) and nonmutated melanoma cases.</p><p>METHODS: Melanoma-prone families participating in this study were identified through a nationwide predictive program starting in 1987. Information on cancer diagnoses (types, stages, and dates) and deaths (causes and dates) were obtained through the Swedish Cancer Registry and Cause of Death Registry. Kaplan Meier and Cox proportional hazards regression models were used to assess survival in CDKN2A(mut) (n = 96) and CDKN2A(wt) (n = 377) familial melanoma cases and in matched sporadic melanoma cases (n = 1042). All statistical tests were two-sided.</p><p>RESULTS: When comparing CDKN2A(mut) and CDKN2A(wt) melanoma cases, after adjusting for age, sex, and T classification, CDKN2A(mut) had worse survival than melanoma (hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.49 to 4.21) and than nonmelanoma cancers (HR = 7.77, 95% CI = 3.65 to 16.51). Compared with matched sporadic cases, CDKN2A(mut) cases had statistically significantly worse survival from both melanoma and nonmelanoma cancers while no differences in survival were seen in CDKN2A(wt) compared with sporadic cases.</p><p>CONCLUSIONS: CDKN2A(mut) cases had statistically significantly worse survival than nonmelanoma cancers and, intriguingly, also from melanoma, compared with melanoma cases with no CDKN2A mutations. Further studies are required to elucidate possible mechanisms behind increased carcinogen susceptibility and the more aggressive melanoma phenotype in CDKN2A mutation carriers.</p>},
  author       = {Helgadottir, Hildur and Höiom, Veronica and Tuominen, Rainer and Nielsen, Kari and Jönsson, Göran B and Olsson, Håkan and Hansson, Johan},
  issn         = {1460-2105},
  language     = {eng},
  number       = {11},
  publisher    = {ARRAY(0x7ff73a8)},
  series       = {Journal of the National Cancer Institute},
  title        = {Germline CDKN2A Mutation Status and Survival in Familial Melanoma Cases},
  url          = {http://dx.doi.org/10.1093/jnci/djw135},
  volume       = {108},
  year         = {2016},
}