Genome-wide association study identifies three new melanoma susceptibility loci.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Barrett, JH; Iles, MM; Harland, M; Taylor, JC; Aitken, JF; Andresen, PA; Akslen, LA; Armstrong, BK; Avril, M-F; Azizi, E; Bakker, B; Bergman, W; Bianchi-Scarrà, G; Bressac-de Paillerets, B; Calista, D; Cannon-Albright, LA; Corda, E; Cust, AE; Dębniak, T; Duffy, D; Dunning, AM; Easton, DF; Friedman, E; Galan, P; Ghiorzo, P; Giles, GG; Hansson, J; Hocevar, M; Höiom, V; Hopper, JL; Ingvar, C; Janssen, B; Jenkins, MA; Jönsson, G; Kefford, RF; Landi, G; Landi, MT; Lang, J; Lubiński, J; Mackie, R; Malvehy, J; Martin, NG; Molven, A; Montgomery, GW; van Nieuwpoort, FA; Novakovic, S; Olsson, H; Pastorino, L; Puig, S; Puig-Butille, JA; Randerson-Moor, J; Snowden, H; Tuominen, R; Van Belle, P; van der Stoep, N; Whiteman, DC; Zelenika, D; Han, J; Fang, S; Lee, JE; Wei, Q; Lathrop, GM; Gillanders, EM; Brown, KM; Goldstein, AM; Kanetsky, PA; Mann, GJ; Macgregor, S; Elder, DE; Amos, CI; Hayward, NK; Gruis, NA; Demenais, F; Bishop, JAN; Bishop, DT; GenoMEL Consortium,

Published Date

  • October 9, 2011

Published In

Volume / Issue

  • 43 / 11

Start / End Page

  • 1108 - 1113

PubMed ID

  • 21983787

Pubmed Central ID

  • 21983787

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.959


  • eng

Conference Location

  • United States