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Br J Dermatol. 2016 Jun;174(6):1308-17. doi: 10.1111/bjd.14407. Epub 2016 Apr 26.

Characterization of patients at high risk of melanoma in Austria.

Author information

1
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
2
The Scripps Research Institute, La Jolla, CA, U.S.A.
3
Clinical Institute for Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
4
Department of Dermatology and Venereology, General Hospital Linz, Linz, Austria.
5
Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.
6
Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.

Abstract

BACKGROUND:

Risk of melanoma is determined by genetic and exogenous factors. Only a few studies have included both characteristics in a comprehensive multivariable analysis.

OBJECTIVES:

To find determinants of patients at high risk of melanoma in Austria, including phenotype, genotype and lifestyle characteristics in comprehensive analyses.

METHODS:

In total, 1668 patients with melanoma from the M3 case-control study were studied. Overall, 567 participants were sequenced for CDKN2A, 232 for CDK4, 123 for MITF encoding the variant E318K and 964 for MC1R.

RESULTS:

Patients with melanoma with a positive family history (n = 190, 11·6%), multiple primary melanomas (n = 261, 15·7%) and younger age (< 50 years, n = 675, 40·5%) were defined as being at high risk. All other patients with melanoma were defined as the reference group. We found significant differences between those two groups and between the high-risk subgroups (positive family history, multiple primary melanomas and younger age). Pigmentation phenotype was associated with the high-risk group in general (childhood freckling, odds ratio 1·46, P = 0·007; blond/reddish hair colour, odds ratio 1·43, P = 0·011). Patients with a positive family history and patients with early-onset disease were similar regarding both their phenotypic characteristics and external factors. Established high-risk mutations in CDKN2A were found in cases with a positive family history (n = 12) or multiple melanomas (n = 2). Moreover, we found three patients carrying the MITF p.E318K variant, two with a CDK4 variant and seven with nonsynonymous MC1R variants with undescribed biological significance, of which four were predicted as damaging.

CONCLUSIONS:

Austrian patients could represent a reservoir for novel genetic variants. Further investigation of populations in Central and Eastern Europe might reveal more novel and disease-relevant variants.

PMID:
26800492
DOI:
10.1111/bjd.14407
[Indexed for MEDLINE]

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