Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.
In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.
Tenesa
Albert
A
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Edinburgh EH4 2XU, UK.
Farrington
Susan M
SM
Prendergast
James G D
JG
Porteous
Mary E
ME
Walker
Marion
M
Haq
Naila
N
Barnetson
Rebecca A
RA
Theodoratou
Evropi
E
Cetnarskyj
Roseanne
R
Cartwright
Nicola
N
Semple
Colin
C
Clark
Andrew J
AJ
Reid
Fiona J L
FJ
Smith
Lorna A
LA
Kavoussanakis
Kostas
K
Koessler
Thibaud
T
Pharoah
Paul D P
PD
Buch
Stephan
S
Schafmayer
Clemens
C
Tepel
Jürgen
J
Schreiber
Stefan
S
Völzke
Henry
H
Schmidt
Carsten O
CO
Hampe
Jochen
J
Chang-Claude
Jenny
J
Hoffmeister
Michael
M
Brenner
Hermann
H
Wilkening
Stefan
S
Canzian
Federico
F
Capella
Gabriel
G
Moreno
Victor
V
Deary
Ian J
IJ
Starr
John M
JM
Tomlinson
Ian P M
IP
Kemp
Zoe
Z
Howarth
Kimberley
K
Carvajal-Carmona
Luis
L
Webb
Emily
E
Broderick
Peter
P
Vijayakrishnan
Jayaram
J
Houlston
Richard S
RS
Rennert
Gad
G
Ballinger
Dennis
D
Rozek
Laura
L
Gruber
Stephen B
SB
Matsuda
Koichi
K
Kidokoro
Tomohide
T
Nakamura
Yusuke
Y
Zanke
Brent W
BW
Greenwood
Celia M T
CM
Rangrej
Jagadish
J
Kustra
Rafal
R
Montpetit
Alexandre
A
Hudson
Thomas J
TJ
Gallinger
Steven
S
Campbell
Harry
H
Dunlop
Malcolm G
MG
D000328:Adult; D000368:Aged; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk