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Journal of the American Academy of Dermatology
Volume 77, n° 5
pages 893-901 (novembre 2017)
Doi : 10.1016/j.jaad.2017.05.050
accepted : 28 May 2017
Original Articles

Cancer risks and survival in patients with multiple primary melanomas: Association with family history of melanoma and germline CDKN2A mutation status
 

Hildur Helgadottir, MD, PhD a, , Rainer Tuominen, PhD a, Håkan Olsson, MD, PhD b, Johan Hansson, MD, PhD a, Veronica Höiom, PhD a
a Department of Oncology-Pathology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden 
b Department of Oncology, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden 

Correspondence to: Hildur Helgadottir, MD, PhD, Department of Oncology Pathology, Karolinska Institutet and Karolinska University Hospital, Solna 171 76 Stockholm, Sweden.Department of Oncology PathologyKarolinska Institutet and Karolinska University HospitalSolna 171 76StockholmSweden
Abstract
Background

Worse outcomes have been noted in patients with multiple primary melanomas (MPMs) than in patients with single primary melanomas.

Objective

We investigated how family history of melanoma and germline CDKN2A mutation status of MPM patients affects risks of developing subsequent melanomas and other cancers and survival outcomes.

Methods

Comprehensive data on cancer diagnoses and deaths of MPM patients, their first-degree relatives, and matched controls were obtained through Swedish national health care and population registries.

Results

Familial MPM cases with germline CDKN2A mutations were youngest at the diagnosis of their second melanoma (median age 42 years) and had among the MPM cohorts the highest relative risks (RR) compared to controls of developing >2 melanomas (RR 238.4, 95% CI 74.8-759.9). CDKN2A mutated MPM cases and their first-degree relatives were the only cohorts with increased risks of nonskin cancers compared to controls (RR 3.6, 95% CI 1.9-147.1 and RR 3.2, 95% CI 1.9-5.6, respectively). In addition, CDKN2A mutated MPM cases had worse survival compared with both cases with familial (HR 3.0, 95% CI 1.3-8.1) and sporadic wild-type MPM (HR 2.63, 95% CI 1.3-5.4).

Limitations

Our study examined outcomes in subgroups of MPM patients, which affected the sample size of the study groups.

Conclusion

This study demonstrates that CDKN2A mutation status and family history of melanoma significantly affects outcomes of MPM patients.

The full text of this article is available in PDF format.

Key words : cancer risk, CDKN2A , familial melanoma, multiple primary melanoma, mutation testing, survival

Abbreviations used : CI, HR, MPM, RR



 Funding sources: Supported by grants from the Swedish Cancer Society (CAN 2013/637 and CAN 2014/851), a Radiumhemmet research fund (144073), and regional and hospital funds in Lund and Stockholm.
 Conflicts of interest: None declared.
 Reprints not available from the authors.



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