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Characterization of patients at high risk of melanoma in Austria
Author(s) -
Müller C.,
Wendt J.,
Rauscher S.,
BurgstallerMuehlbacher S.,
SunderPlassmann R.,
Scheurecker C.,
Richtig E.,
Fae I.,
Fischer G.,
Pehamberger H.,
Okamoto I.
Publication year - 2016
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.14407
Subject(s) - cdkn2a , melanoma , family history , odds ratio , medicine , microphthalmia associated transcription factor , genotype , oncology , cancer , genetics , biology , gene , cancer research , transcription factor
Summary 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 CDKN 2A , 232 for CDK 4 , 123 for MITF encoding the variant E318K and 964 for MC 1R . 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 CDKN 2A 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 CDK 4 variant and seven with nonsynonymous MC 1R 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.