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Genome-wide association study identifies three new melanoma susceptibility loci
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
Affiliation:Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Leeds Cancer Research UK Centre, St James’s University Hospital, Leeds, UK.
Abstract: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.
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