Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer.
Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4; P = 8.1 x 10(-10)), 16q22.1 (rs9929218, CDH1; P = 1.2 x 10(-8)), 19q13.1 (rs10411210, RHPN2; P = 4.6 x 10(-9)) and 20p12.3 (rs961253; P = 2.0 x 10(-10)). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.
Houlston
Richard S
RS
Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK. richard.houlston@icr.ac.uk
Webb
Emily
E
Broderick
Peter
P
Pittman
Alan M
AM
Di Bernardo
Maria Chiara
MC
Lubbe
Steven
S
Chandler
Ian
I
Vijayakrishnan
Jayaram
J
Sullivan
Kate
K
Penegar
Steven
S
Carvajal-Carmona
Luis
L
Howarth
Kimberley
K
Jaeger
Emma
E
Spain
Sarah L
SL
Walther
Axel
A
Barclay
Ella
E
Martin
Lynn
L
Gorman
Maggie
M
Domingo
Enric
E
Teixeira
Ana S
AS
Kerr
David
D
Cazier
Jean-Baptiste
JB
Niittymäki
Iina
I
Tuupanen
Sari
S
Karhu
Auli
A
Aaltonen
Lauri A
LA
Tomlinson
Ian P M
IP
Farrington
Susan M
SM
Tenesa
Albert
A
Prendergast
James G D
JG
Barnetson
Rebecca A
RA
Cetnarskyj
Roseanne
R
Porteous
Mary E
ME
Pharoah
Paul D P
PD
Koessler
Thibaud
T
Hampe
Jochen
J
Buch
Stephan
S
Schafmayer
Clemens
C
Tepel
Jurgen
J
Schreiber
Stefan
S
Völzke
Henry
H
Chang-Claude
Jenny
J
Hoffmeister
Michael
M
Brenner
Hermann
H
Zanke
Brent W
BW
Montpetit
Alexandre
A
Hudson
Thomas J
TJ
Gallinger
Steven
S
Campbell
Harry
H
Dunlop
Malcolm G
MG
D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged