Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk.
We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK. malcolm.dunlop@hgu.mrc.ac.uk
Malcolm G
MG
Dunlop
Sara E
SE
Dobbins
Susan Mary
SM
Farrington
Angela M
AM
Jones
Claire
C
Palles
Nicola
N
Whiffin
Albert
A
Tenesa
Sarah
S
Spain
Peter
P
Broderick
Li-Yin
LY
Ooi
Enric
E
Domingo
Claire
C
Smillie
Marc
M
Henrion
Matthew
M
Frampton
Lynn
L
Martin
Graeme
G
Grimes
Maggie
M
Gorman
Colin
C
Semple
Yusanne P
YP
Ma
Ella
E
Barclay
James
J
Prendergast
Jean-Baptiste
JB
Cazier
Bianca
B
Olver
Steven
S
Penegar
Steven
S
Lubbe
Ian
I
Chander
Luis G
LG
Carvajal-Carmona
Stephane
S
Ballereau
Amy
A
Lloyd
Jayaram
J
Vijayakrishnan
Lina
L
Zgaga
Igor
I
Rudan
Evropi
E
Theodoratou
John M
JM
Starr
Ian
I
Deary
Iva
I
Kirac
Dujo
D
Kovacević
Lauri A
LA
Aaltonen
Laura
L
Renkonen-Sinisalo
Jukka-Pekka
JP
Mecklin
Koichi
K
Matsuda
Yusuke
Y
Nakamura
Yukinori
Y
Okada
Steven
S
Gallinger
David J
DJ
Duggan
David
D
Conti
Polly
P
Newcomb
John
J
Hopper
Mark A
MA
Jenkins
Fredrick
F
Schumacher
Graham
G
Casey
Douglas
D
Easton
Mitul
M
Shah
Paul
P
Pharoah
Annika
A
Lindblom
Tao
T
Liu
Christopher G
CG
Smith
Hannah
H
West
Jeremy P
JP
Cheadle
Rachel
R
Midgley
David J
DJ
Kerr
Harry
H
Campbell
Ian P
IP
Tomlinson
Richard S
RS
Houlston
D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004258:DNA Polymerase III / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008565:Membrane Proteins; C101060:SHROOM2 protein, human; C435720:POLD3 protein, human; D004258:DNA Polymerase III