Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3

• Published in: Nature genetics Vol. 43; no. 11; pp. 1114 - 1118
• Main Authors: MacGregor, Stuart, Montgomery, Grant W, Liu, Jimmy Z, Zhao, Zhen Zhen, Henders, Anjali K, Stark, Mitchell, Schmid, Helen, Holland, Elizabeth A, Duffy, David L, Zhang, Mingfeng, Painter, Jodie N, Nyholt, Dale R, Maskiell, Judith A, Jetann, Jodie, Ferguson, Megan, Cust, Anne E, Jenkins, Mark A, Whiteman, David C, Olsson, Håkan, Puig, Susana, Bianchi-Scarrà, Giovanna, Hansson, Johan, Demenais, Florence, Landi, Maria Teresa, Dębniak, Tadeusz, Mackie, Rona, Azizi, Esther, Bressac-de Paillerets, Brigitte, Goldstein, Alisa M, Kanetsky, Peter A, Gruis, Nelleke A, Elder, David E, Newton-Bishop, Julia A, Bishop, D Timothy, Iles, Mark M, Helsing, Per, Amos, Christopher I, Wei, Qingyi, Wang, Li-E, Lee, Jeffrey E, Qureshi, Abrar A, Kefford, Richard F, Giles, Graham G, Armstrong, Bruce K, Aitken, Joanne F, Han, Jiali, Hopper, John L, Trent, Jeffrey M, Brown, Kevin M, Martin, Nicholas G, Mann, Graham J, Hayward, Nicholas K
• 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; Arrays; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer and Oncology; Cancer och onkologi; Cancer Research; Case studies; Chromosomes, Human, Pair 1; Clinical Medicine; Confidence intervals; Dermatology; Disease susceptibility; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic research; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomes; Genomics; Grants; Human Genetics; Humans; Klinisk medicin; letter; Medical and Health Sciences; Medical research; Medical sciences; Medicin och hälsovetenskap; Melanoma; Melanoma - genetics; Pigmentation; Polymorphism, Single Nucleotide; Principal components analysis; Studies; Tumors of the skin and soft tissue. Premalignant lesions; Sensitivity; Association; Susceptibility locus; Malignant melanoma; Identification; Malignant tumor; Cancer
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.958

Stuart MacGregor and colleagues report the results of a genome-wide association study for melanoma susceptibility in an Australian population. They identify a new melanoma susceptibility locus on chromosome 1. We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R , ASIP and MTAP – CDKN2A . We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10 −11 , OR in combined replication cohorts of 0.89 (95% CI 0.85–0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10 −8 ). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1 . Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.