Journal Article

Genome-wide association study identifies three loci associated with melanoma risk

Kefford, Richard F, Newton Bishop, Julia A, Höiom, Veronica, Calista, Donato, Novakovic, Srdjan, Aitken, Joanne F, Puig, Susana, Gillanders, Elizabeth M, Avril, Marie-Francoise, Boland, Anne, Barrett, Jennifer H, Montgomery, Grant W, Hansson, Johan, Bianchi-Scarrà, Giovanna, Demenais, Florence, Dębniak, Tadeusz, Corda, Eve, Cannon-Albright, Lisa A, Hopper, John L, Goldstein, Alisa M, Gruis, Nelleke A, van Nieuwpoort, Frans A, Iles, Mark M, Mann, Graham J, Mackie, Rona, Hayward, Nicholas K, van Workum, Wilbert, Zelenika, Diana, Lang, Julie, Malvehy, Josep, Lubiński, Jan, Bakker, Bert, Harland, Mark, Azizi, Esther, Chin-A-Woeng, Thomas, Brown, Kevin M, Ingvar, Christian, Martin, Nicholas G, Randerson-Moor, Juliette, Bressac-de Paillerets, Brigitte, Ghiorzo, Paola, Lathrop, G Mark, Galan, Pilar, Landi, Maria Teresa, Kanetsky, Peter A, Bishop, D Timothy, Gut, Ivo, Elder, David E, Galore-Haskel, Gilli, Hočevar, Marko, Taylor, John C, Weiss, Marjan, Olsson, Håkan

2009

Overview

Timothy Bishop and colleagues from GenoMEL present a genome-wide association study for melanoma. They report three loci associated with susceptibility to melanoma, of which two were previously associated with pigmentation. We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P < 5 × 10 −7 . Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 × 10 −27 for rs258322), 11q14-q21 encompassing TYR ( P = 2.41 × 10 −14 for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A ( P = 4.03 × 10 −7 for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Agriculture / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer and Oncology / Cancer och onkologi / Cancer Research / Cell cycle / Chromosomes / Clinical Medicine / Confidence intervals / Data collection / Dermatology / Fundamental and applied biological sciences. Psychology / Gene Function / Gene loci / Genetic aspects / Genetic Predisposition to Disease - genetics / Genetic variance / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study / Geography / Health risks / Human Genetics / Humans / Identification and classification / Klinisk medicin / letter / Medical and Health Sciences / Medical sciences / Medicin och hälsovetenskap / Melanoma / Melanoma - genetics / Pigmentation / Polymorphism, Single Nucleotide - genetics / Principal components analysis / Quantitative trait loci / Regression analysis / Reproducibility of Results / Risk factors / Single nucleotide polymorphisms / Tumors of the skin and soft tissue. Premalignant lesions / Ultraviolet radiation