1. Comprehensive Field Synopsis and Systematic Meta-analyses of Genetic Association Studies in Cutaneous Melanoma
- Author
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George M. Spyrou, Johannes T. Roehr, Vasiliki Nicolaou, Elizabeth Kodela, Andreas Katsambas, Evangelos Evangelou, Foteini Chatzinasiou, Katerina P. Kypreou, Christina M. Lill, John P. A. Ioannidis, I. Stefanaki, Hensin Tsao, Lars Bertram, and Alexander J. Stratigos more...
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Cancer Research ,Candidate gene ,Skin Neoplasms ,basal-cell carcinoma ,Genome-wide association study ,Review ,Neoplasm Proteins/genetics ,Gene Frequency ,CDKN2A ,Databases, Genetic ,Membrane Transport Proteins/genetics ,familial melanoma ,Melanoma ,Genetics ,Molecular Epidemiology ,Membrane Glycoproteins ,biology ,DNA-repair ,Confounding ,Oxidoreductases/genetics ,Confounding Factors, Epidemiologic ,Neoplasm Proteins ,Antigens, Neoplasm/genetics ,Oncology ,Research Design ,knowledge-base ,Agouti Signaling Protein ,Oxidoreductases ,Receptor, Melanocortin, Type 1 ,SLC45A2 ,Genotype ,Locus (genetics) ,Receptor, Melanocortin, Type 1/genetics ,skin-cancer ,Polymorphism, Single Nucleotide ,Receptors, Calcitriol/genetics ,Myosin Heavy Chains/genetics ,Cyclin-Dependent Kinase Inhibitor p16/genetics ,Meta-Analysis as Topic ,Antigens, Neoplasm ,Agouti Signaling Protein/genetics ,Cardiac Myosins/genetics ,Humans ,Membrane Proteins/genetics ,Allele frequency ,Cyclin-Dependent Kinase Inhibitor p16 ,Genetic association ,sequence variants ,human pigmentation ,Myosin Heavy Chains ,Membrane Proteins ,Membrane Transport Proteins ,Reproducibility of Results ,Membrane Glycoproteins/genetics ,receptor mc1r gene ,Confounding Factors (Epidemiology) ,Melanoma/*epidemiology/*genetics ,genome-wide association ,biology.protein ,Receptors, Calcitriol ,Skin Neoplasms/*epidemiology/*genetics ,malignant-melanoma ,Cardiac Myosins ,Genome-Wide Association Study - 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 x 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. J Natl Cancer Inst more...
- Published
- 2011
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