title: Comprehensive field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma.
abstract: BACKGROUND
  Although genetic studies have reported a number of loci associated with cutaneous melanoma (CM) risk, a comprehensive synopsis of genetic association studies published in the field and systematic meta-analysis for all eligible polymorphisms have not been reported.
  
  
  METHODS
  We systematically annotated data from all genetic association studies published in the CM field (n = 145), including data from genome-wide association studies (GWAS), and performed random-effects meta-analyses across all eligible polymorphisms on the basis of four or more independent case-control datasets in the main analyses. Supplementary analyses of three available datasets derived from GWAS and GWAS-replication studies were also done. Nominally statistically significant associations between polymorphisms and CM were graded for the strength of epidemiological evidence on the basis of the Human Genome Epidemiology Network Venice criteria. All statistical tests were two-sided.
  
  
  RESULTS
  Forty-two polymorphisms across 18 independent loci evaluated in four or more datasets including candidate gene studies and available GWAS data were subjected to meta-analysis. Eight loci were identified in the main meta-analyses as being associated with a risk of CM (P < .05) of which four loci showed a genome-wide statistically significant association (P < 1 × 10(-7)), including 16q24.3 (MC1R), 20q11.22 (MYH7B/PIGU/ASIP), 11q14.3 (TYR), and 5p13.2 (SLC45A2). Grading of the cumulative evidence by the Venice criteria suggested strong epidemiological credibility for all four loci with genome-wide statistical significance and one additional gene at 9p23 (TYRP1). In the supplementary meta-analyses, a locus at 9p21.3 (CDKN2A/MTAP) reached genome-wide statistical significance with CM and had strong epidemiological credibility.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first comprehensive field synopsis and systematic meta-analysis to identify genes associated with an increased susceptibility to CM.
authors.affiliation: Department of Dermatology, University of Athens Medical School, Andreas Sygros Hospital, Dragoumi 5, Athens 161 21, Greece.
authors.forename: Foteini
authors.initials: F
authors.lastname: Chatzinasiou
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lill
authors.forename: Katerina
authors.initials: K
authors.lastname: Kypreou
authors.forename: Irene
authors.initials: I
authors.lastname: Stefanaki
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Nicolaou
authors.forename: George
authors.initials: G
authors.lastname: Spyrou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Evangelou
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Roehr
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kodela
authors.forename: Andreas
authors.initials: A
authors.lastname: Katsambas
authors.forename: Hensin
authors.initials: H
authors.lastname: Tsao
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stratigos
mesh_terms: D054366:Agouti Signaling Protein / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D024722:Cardiac Myosins / Q000235:genetics; D015986:Confounding Factors, Epidemiologic; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D030541:Databases, Genetic; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008545:Melanoma / Q000453:epidemiology* / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D015201:Meta-Analysis as Topic; D017720:Molecular Epidemiology; D018995:Myosin Heavy Chains / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D015203:Reproducibility of Results; D012107:Research Design; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000235:genetics*
chemical_list: C515182:ASIP protein, human; D054366:Agouti Signaling Protein; D000951:Antigens, Neoplasm; C422445:CLPTM1L protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C501641:MYH7 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D044102:Receptor, Melanocortin, Type 1; D018167:Receptors, Calcitriol; C510061:SLC45A2 protein, human; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains