title: Updated field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma: the MelGene database.
abstract: We updated a field synopsis of genetic associations of cutaneous melanoma (CM) by systematically retrieving and combining data from all studies in the field published as of August 31, 2013. Data were available from 197 studies, which included 83,343 CM cases and 187,809 controls and reported on 1,126 polymorphisms in 289 different genes. Random-effects meta-analyses of 81 eligible polymorphisms evaluated in >4 data sets confirmed 20 single-nucleotide polymorphisms across 10 loci (TYR, AFG3L1P, CDK10, MYH7B, SLC45A2, MTAP, ATM, CLPTM1L, FTO, and CASP8) that have previously been published with genome-wide significant evidence for association (P<5 × 10(-8)) with CM risk, with certain variants possibly functioning as proxies of already tagged genes. Four other loci (MITF, CCND1, MX2, and PLA2G6) were also significantly associated with 5 × 10(-8)<P<1 × 10(-3). In supplementary meta-analyses derived from genome-wide association studies, one additional locus located 11 kb upstream of ARNT (chromosome 1q21) showed genome-wide statistical significance with CM. Our approach serves as a useful model in analyzing and integrating the reported germline alterations involved in CM.
authors.affiliation: Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital, Athens, Greece.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Antonopoulou
authors.affiliation: Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital, Athens, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Stefanaki
authors.affiliation: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany; Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lill
authors.affiliation: Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital, Athens, Greece.
authors.forename: Foteini
authors.initials: F
authors.lastname: Chatzinasiou
authors.affiliation: Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital, Athens, Greece.
authors.forename: Katerina P
authors.initials: KP
authors.lastname: Kypreou
authors.affiliation: Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital, Athens, Greece.
authors.forename: Fani
authors.initials: F
authors.lastname: Karagianni
authors.affiliation: Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Athanasiadis
authors.affiliation: Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
authors.forename: George M
authors.initials: GM
authors.lastname: Spyrou
authors.affiliation: Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: John P A
authors.initials: JPA
authors.lastname: Ioannidis
authors.affiliation: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany; Department of Medicine, School of Public Health, Imperial College London, London, UK.
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.affiliation: Department of Hygiene and Epidemiology, Clinical and Molecular Epidemiology Unit, School of Medicine, University of Ioannina, Ioannina, Greece; Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, London, UK.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Evangelou
authors.affiliation: Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital, Athens, Greece. Electronic address: alstrat@hol.gr.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stratigos
mesh_terms: D002874:Chromosome Mapping; D030541:Databases, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D018095:Germ-Line Mutation; D006801:Humans; D015810:Linkage Disequilibrium; D008545:Melanoma / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms / Q000235:genetics*; D000096142:Cutaneous Malignant Melanoma