학술논문
Genome-wide association study identifies three new melanoma susceptibility loci.
Document Type
Article
Author
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; D?bniak, Tadeusz; Duffy, David
Source
Subject
*MELANOMA diagnosis
*DISEASE susceptibility
*GENETIC polymorphisms
*GENOTYPE-environment interaction
*PHENOTYPES
*EUROPEANS
*HEALTH
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Language
ISSN
1061-4036
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. [ABSTRACT FROM AUTHOR]