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CDKN2a mutation-negative melanoma families have increased risk exclusively for skin cancers but not for other malignancies.

Helgadottir, Hildur; Höiom, Veronica; Tuominen, Rainer; Jönsson, Göran B LU ; Månsson-Brahme, Eva; Olsson, Håkan LU and Hansson, Johan (2015) In International Journal of Cancer 137(9). p.2220-2226
Abstract
Germline CDKN2A mutations are found in 5-20% of melanoma families. Numerous studies have shown that carriers of CDKN2A mutations have increased risks of non-melanoma cancers, but so far there have been no studies investigating cancer risks in CDKN2A wild type (wt) melanoma families. In this prospective cohort study, index melanoma cases (n = 224) and their first-degree relatives (n = 944) were identified from 154 confirmed CDKN2A wt melanoma families. Cancer diagnoses in family members and matched controls were obtained from the Swedish Cancer Registry. Relative risks (RR), odds ratios (OR) and two-sided 95% confidence intervals (95% CI) were calculated. In index cases and first-degree relatives, the prospective RR for melanoma was 56.9... (More)
Germline CDKN2A mutations are found in 5-20% of melanoma families. Numerous studies have shown that carriers of CDKN2A mutations have increased risks of non-melanoma cancers, but so far there have been no studies investigating cancer risks in CDKN2A wild type (wt) melanoma families. In this prospective cohort study, index melanoma cases (n = 224) and their first-degree relatives (n = 944) were identified from 154 confirmed CDKN2A wt melanoma families. Cancer diagnoses in family members and matched controls were obtained from the Swedish Cancer Registry. Relative risks (RR), odds ratios (OR) and two-sided 95% confidence intervals (95% CI) were calculated. In index cases and first-degree relatives, the prospective RR for melanoma was 56.9 (95% CI 31.4-102.1) and 7.0 (95% CI 4.2-11.4), respectively, and for squamous cell skin cancers 9.1 (95% CI 6.0-13.7) and 3.4 (95% CI 2.2-5.2), respectively. In neither group, elevated risks were seen for non-skin cancers. In a subgroup analysis, CDKN2A wt melanoma families with young (<40 years) melanoma cases were found to have increased risk of non-skin cancers (RR 1.5, 95% CI 1.0-1.5). Further, MC1R gene variants were increased in familial melanoma cases compared to controls (OR 2.4, 95% CI 1.6-3.4). Our findings suggest that in the majority of CDKN2A wt melanoma families, a segregation of variants in low-risk melanoma genes such as MC1R causes increased skin cancer susceptibility, rather than mutations in high-risk cancer predisposing genes, such mutations are more probable to be found in melanoma families with young melanoma cases. This study further supports an implication of CDKN2A mutation screening as a clinical test that determines counseling and follows up routines of melanoma families. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
International Journal of Cancer
volume
137
issue
9
pages
2220 - 2226
publisher
John Wiley & Sons
external identifiers
  • pmid:25943250
  • wos:000359782700020
  • scopus:84939253160
ISSN
0020-7136
DOI
10.1002/ijc.29595
language
English
LU publication?
yes
id
f02665cb-6867-4b87-9a84-c4423928ede6 (old id 5456955)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25943250?dopt=Abstract
date added to LUP
2015-06-02 15:16:32
date last changed
2017-10-29 03:16:53
@article{f02665cb-6867-4b87-9a84-c4423928ede6,
  abstract     = {Germline CDKN2A mutations are found in 5-20% of melanoma families. Numerous studies have shown that carriers of CDKN2A mutations have increased risks of non-melanoma cancers, but so far there have been no studies investigating cancer risks in CDKN2A wild type (wt) melanoma families. In this prospective cohort study, index melanoma cases (n = 224) and their first-degree relatives (n = 944) were identified from 154 confirmed CDKN2A wt melanoma families. Cancer diagnoses in family members and matched controls were obtained from the Swedish Cancer Registry. Relative risks (RR), odds ratios (OR) and two-sided 95% confidence intervals (95% CI) were calculated. In index cases and first-degree relatives, the prospective RR for melanoma was 56.9 (95% CI 31.4-102.1) and 7.0 (95% CI 4.2-11.4), respectively, and for squamous cell skin cancers 9.1 (95% CI 6.0-13.7) and 3.4 (95% CI 2.2-5.2), respectively. In neither group, elevated risks were seen for non-skin cancers. In a subgroup analysis, CDKN2A wt melanoma families with young (&lt;40 years) melanoma cases were found to have increased risk of non-skin cancers (RR 1.5, 95% CI 1.0-1.5). Further, MC1R gene variants were increased in familial melanoma cases compared to controls (OR 2.4, 95% CI 1.6-3.4). Our findings suggest that in the majority of CDKN2A wt melanoma families, a segregation of variants in low-risk melanoma genes such as MC1R causes increased skin cancer susceptibility, rather than mutations in high-risk cancer predisposing genes, such mutations are more probable to be found in melanoma families with young melanoma cases. This study further supports an implication of CDKN2A mutation screening as a clinical test that determines counseling and follows up routines of melanoma families.},
  author       = {Helgadottir, Hildur and Höiom, Veronica and Tuominen, Rainer and Jönsson, Göran B and Månsson-Brahme, Eva and Olsson, Håkan and Hansson, Johan},
  issn         = {0020-7136},
  language     = {eng},
  number       = {9},
  pages        = {2220--2226},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {CDKN2a mutation-negative melanoma families have increased risk exclusively for skin cancers but not for other malignancies.},
  url          = {http://dx.doi.org/10.1002/ijc.29595},
  volume       = {137},
  year         = {2015},
}