title: Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score.
abstract: Many single nucleotide polymorphisms (SNPs) have been described as putative risk factors for melanoma. The aim of our study was to validate the most prominent genetic risk loci in an independent Greek melanoma case-control dataset and to assess their cumulative effect solely or combined with established phenotypic risk factors on individualized risk prediction. We genotyped 59 SNPs in 800 patients and 800 controls and tested their association with melanoma using logistic regression analyses. We constructed a weighted genetic risk score (GRSGWS) based on SNPs that showed genome-wide significant (GWS) association with melanoma in previous studies and assessed their impact on risk prediction. Fifteen independent SNPs from 12 loci were significantly associated with melanoma (P < 0.05). Risk score analysis yielded an odds ratio of 1.36 per standard deviation increase of the GRSGWS (P = 1.1 × 10(-7)). Individuals in the highest 20% of the GRSGWS had a 1.88-fold increase in melanoma risk compared with those in the middle quintile. By adding the GRSGWS to a phenotypic risk model, the C-statistic increased from 0.764 to 0.775 (P = 0.007). In summary, the GRSGWS is associated with melanoma risk and achieves a modest improvement in risk prediction when added to a phenotypic risk model.
authors.affiliation: 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Katerina P
authors.initials: KP
authors.lastname: Kypreou
authors.affiliation: 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Stefanaki
authors.affiliation: 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Antonopoulou
authors.affiliation: 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Fani
authors.initials: F
authors.lastname: Karagianni
authors.affiliation: Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece, GR.
authors.forename: Georgios
authors.initials: G
authors.lastname: Ntritsos
authors.affiliation: 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Alexios
authors.initials: A
authors.lastname: Zaras
authors.affiliation: 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Nikolaou
authors.affiliation: Blood Donation Unit, Laikon Hospital, Athens, Greece.
authors.forename: Iro
authors.initials: I
authors.lastname: Kalfa
authors.affiliation: 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Chasapi
authors.affiliation: 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Polydorou
authors.affiliation: Department of Internal Medicine, University of Athens, Laikon Hospital, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Gogas
authors.affiliation: Biomedical Informatics Unit, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
authors.forename: George M
authors.initials: GM
authors.lastname: Spyrou
authors.affiliation: Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lill
authors.affiliation: Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, and Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, USA.
authors.forename: John P A
authors.initials: JPA
authors.lastname: Ioannidis
authors.affiliation: 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Antoniou
authors.affiliation: Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece, GR; Department of Epidemiology and Biostatistics, Imperial College London, St. Mary's Campus, London, United Kingdom.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Evangelou
authors.affiliation: 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: alstrat@hol.gr.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Stratigos
mesh_terms: D000704:Analysis of Variance; D003430:Cross-Sectional Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008545:Melanoma / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology