Germline CDKN2A Mutation Status and Survival in Familial Melanoma Cases
Författare
Summary, in English
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.
Avdelning/ar
- Dermatologi och venereologi, Lund
- Bröstcancer-genetik
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Lunds Melanomstudiegrupp
- Tumörmikromiljö
- Medicinsk onkologi
- EpiHealth: Epidemiology for Health
Publiceringsår
2016-11
Språk
Engelska
Publikation/Tidskrift/Serie
Journal of the National Cancer Institute
Volym
108
Issue
11
Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Cancer and Oncology
Status
Published
Forskningsgrupp
- Lund Melanoma Study Group
ISBN/ISSN/Övrigt
- ISSN: 1460-2105