Genome-wide association study identifies three new melanoma susceptibility loci

• Published in: Nature genetics Vol. 43; no. 11; pp. 1108 - 1113
• Main Authors: Barrett, Jennifer H, Iles, Mark M, Harland, Mark, Taylor, John C, Aitken, Joanne F, Andresen, Per Arne, Akslen, Lars A, Armstrong, Bruce K, Avril, Marie-Francoise, Azizi, Esther, Bakker, Bert, Bergman, Wilma, Bianchi-Scarrà, Giovanna, Bressac-de Paillerets, Brigitte, Calista, Donato, Cannon-Albright, Lisa A, Corda, Eve, Cust, Anne E, Dębniak, Tadeusz, Duffy, David, Dunning, Alison M, Easton, Douglas F, Friedman, Eitan, Galan, Pilar, Ghiorzo, Paola, Giles, Graham G, Hansson, Johan, Hocevar, Marko, Höiom, Veronica, Hopper, John L, Ingvar, Christian, Janssen, Bart, Jenkins, Mark A, Jönsson, Göran, Kefford, Richard F, Landi, Giorgio, Landi, Maria Teresa, Lang, Julie, Lubiński, Jan, Mackie, Rona, Malvehy, Josep, Martin, Nicholas G, Molven, Anders, Montgomery, Grant W, van Nieuwpoort, Frans A, Novakovic, Srdjan, Olsson, Håkan, Pastorino, Lorenza, Puig, Susana, Puig-Butille, Joan Anton, Randerson-Moor, Juliette, Snowden, Helen, Tuominen, Rainer, Van Belle, Patricia, van der Stoep, Nienke, Whiteman, David C, Zelenika, Diana, Han, Jiali, Fang, Shenying, Lee, Jeffrey E, Wei, Qingyi, Lathrop, G Mark, Gillanders, Elizabeth M, Brown, Kevin M, Goldstein, Alisa M, Kanetsky, Peter A, Mann, Graham J, MacGregor, Stuart, Elder, David E, Amos, Christopher I, Hayward, Nicholas K, Gruis, Nelleke A, Demenais, Florence, Bishop, Julia A Newton, Bishop, D Timothy
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2011; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/727/2000; 692/699/67/1813/1634; Agriculture; Analysis; Animal Genetics and Genomics; Awards & honors; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer and Oncology; Cancer och onkologi; Cancer Research; Case-Control Studies; Chromosomes; Clinical Medicine; Càncer de pell; Dermatology; Disease susceptibility; Family medical history; Fundamental and applied biological sciences. Psychology; Gene Function; Genealogy; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetic research; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomes; Genomics; Genètica mèdica; Human Genetics; Humans; Kirurgi; Klinisk medicin; letter; Life Sciences; Medical and Health Sciences; Medical genetics; Medical research; Medical sciences; Medicin och hälsovetenskap; Melanoma; Melanoma - genetics; Pigmentation; Polymorphism, Single Nucleotide; Single nucleotide polymorphisms; Skin cancer; Skin Neoplasms - genetics; Statistical analysis; Studies; Surgery; Tumors of the skin and soft tissue. Premalignant lesions; Identification; Malignant tumor; Locus; Malignant melanoma; Cancer; WOMEN; CUTANEOUS MALIGNANT-MELANOMA; POPULATION; METAANALYSIS; GENE; PHENOTYPIC CHARACTERISTICS; RISK; SEQUENCE VARIANTS; CANCER; NEVI
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.959

Timothy Bishop and colleagues of the GenoMEL Consortium report a genome-wide association study for melanoma, identifying three new susceptibility loci. We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10 −5 and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10 −3 : an SNP in ATM (rs1801516, overall P = 3.4 × 10 −9 ), an SNP in MX2 (rs45430, P = 2.9 × 10 −9 ) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10 −10 ). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10 −7 under a fixed-effects model and P = 1.2 × 10 −3 under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.