Genome-wide association study identifies three loci associated with melanoma risk.
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 x 10(-7). Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 x 10(-27) for rs258322), 11q14-q21 encompassing TYR (P = 2.41 x 10(-14) for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 x 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.
Bishop
D Timothy
DT
Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK. d.t.bishop@leeds.ac.uk
Demenais
Florence
F
Iles
Mark M
MM
Harland
Mark
M
Taylor
John C
JC
Corda
Eve
E
Randerson-Moor
Juliette
J
Aitken
Joanne F
JF
Avril
Marie-Francoise
MF
Azizi
Esther
E
Bakker
Bert
B
Bianchi-Scarrà
Giovanna
G
Bressac-de Paillerets
Brigitte
B
Calista
Donato
D
Cannon-Albright
Lisa A
LA
Chin-A-Woeng
Thomas
T
Debniak
Tadeusz
T
Galore-Haskel
Gilli
G
Ghiorzo
Paola
P
Gut
Ivo
I
Hansson
Johan
J
Hocevar
Marko
M
Höiom
Veronica
V
Hopper
John L
JL
Ingvar
Christian
C
Kanetsky
Peter A
PA
Kefford
Richard F
RF
Landi
Maria Teresa
MT
Lang
Julie
J
Lubiński
Jan
J
Mackie
Rona
R
Malvehy
Josep
J
Mann
Graham J
GJ
Martin
Nicholas G
NG
Montgomery
Grant W
GW
van Nieuwpoort
Frans A
FA
Novakovic
Srdjan
S
Olsson
Håkan
H
Puig
Susana
S
Weiss
Marjan
M
van Workum
Wilbert
W
Zelenika
Diana
D
Brown
Kevin M
KM
Goldstein
Alisa M
AM
Gillanders
Elizabeth M
EM
Boland
Anne
A
Galan
Pilar
P
Elder
David E
DE
Gruis
Nelleke A
NA
Hayward
Nicholas K
NK
Lathrop
G Mark
GM
Barrett
Jennifer H
JH
Bishop
Julia A Newton
JA
D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005843:Geography; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results