Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24.
Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.
Zanke
Brent W
BW
Cancer Care Ontario, 620 University Avenue, Toronto, Ontario M5G 1L7, Canada.
Greenwood
Celia M T
CM
Rangrej
Jagadish
J
Kustra
Rafal
R
Tenesa
Albert
A
Farrington
Susan M
SM
Prendergast
James
J
Olschwang
Sylviane
S
Chiang
Theodore
T
Crowdy
Edgar
E
Ferretti
Vincent
V
Laflamme
Philippe
P
Sundararajan
Saravanan
S
Roumy
Stéphanie
S
Olivier
Jean-François
JF
Robidoux
Frédérick
F
Sladek
Robert
R
Montpetit
Alexandre
A
Campbell
Peter
P
Bezieau
Stephane
S
O'Shea
Anne Marie
AM
Zogopoulos
George
G
Cotterchio
Michelle
M
Newcomb
Polly
P
McLaughlin
John
J
Younghusband
Ban
B
Green
Roger
R
Green
Jane
J
Porteous
Mary E M
ME
Campbell
Harry
H
Blanche
Helene
H
Sahbatou
Mourad
M
Tubacher
Emmanuel
E
Bonaiti-Pellié
Catherine
C
Buecher
Bruno
B
Riboli
Elio
E
Kury
Sebastien
S
Chanock
Stephen J
SJ
Potter
John
J
Thomas
Gilles
G
Gallinger
Steven
S
Hudson
Thomas J
TJ
Dunlop
Malcolm G
MG
D016022:Case-Control Studies; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide