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International Journal of Cancer
Article . 2015 . Peer-reviewed
License: Wiley Online Library User Agreement
Data sources: Crossref
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CDKN2a mutation‐negative melanoma families have increased risk exclusively for skin cancers but not for other malignancies

Authors: Hildur, Helgadottir; Veronica, Höiom; Rainer, Tuominen; Göran, Jönsson; Eva, Månsson-Brahme; Håkan, Olsson; Johan, Hansson;

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

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 (<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.

Keywords

Adult, Aged, 80 and over, Risk, Skin Neoplasms, Adolescent, Middle Aged, Young Adult, Carcinoma, Squamous Cell, Humans, Genetic Predisposition to Disease, Prospective Studies, Melanoma, Receptor, Melanocortin, Type 1, Cyclin-Dependent Kinase Inhibitor p16, Genetic Association Studies, Aged

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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    influence
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    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
25
Top 10%
Top 10%
Top 10%
bronze