A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk.
To identify risk variants for colorectal cancer (CRC), we conducted a genome-wide association study, genotyping 550,163 tag SNPs in 940 individuals with familial colorectal tumor (627 CRC, 313 advanced adenomas) and 965 controls. We evaluated selected SNPs in three replication sample sets (7,473 cases, 5,984 controls) and identified three SNPs in SMAD7 (involved in TGF-beta and Wnt signaling) associated with CRC. Across the four sample sets, the association between rs4939827 and CRC was highly statistically significant (P(trend) = 1.0 x 10(-12)).
Broderick
Peter
P
Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK.
Carvajal-Carmona
Luis
L
Pittman
Alan M
AM
Webb
Emily
E
Howarth
Kimberley
K
Rowan
Andrew
A
Lubbe
Steven
S
Spain
Sarah
S
Sullivan
Kate
K
Fielding
Sarah
S
Jaeger
Emma
E
Vijayakrishnan
Jayaram
J
Kemp
Zoe
Z
Gorman
Maggie
M
Chandler
Ian
I
Papaemmanuil
Elli
E
Penegar
Steven
S
Wood
Wendy
W
Sellick
Gabrielle
G
Qureshi
Mobshra
M
Teixeira
Ana
A
Domingo
Enric
E
Barclay
Ella
E
Martin
Lynn
L
Sieber
Oliver
O
Kerr
David
D
Gray
Richard
R
Peto
Julian
J
Cazier
Jean-Baptiste
JB
Tomlinson
Ian
I
Houlston
Richard S
RS
D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051906:Smad7 Protein / Q000235:genetics*
C497806:SMAD7 protein, human; D051906:Smad7 Protein