Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer.
The common single-nucleotide polymorphism (SNP) rs3802842 at 11q23.1 has recently been reported to be associated with risk of colorectal cancer (CRC). To examine this association in detail we genotyped rs3802842 in eight independent case-control series comprising a total of 10 638 cases and 10 457 healthy individuals. A significant association between the C allele of rs3802842 and CRC risk was found (per allele OR = 1.17; 95% confidence interval [CI]: 1.12-1.22; P = 1.08 x 10(-12)) with the risk allele more frequent in rectal than colonic disease (P = 0.02). In combination with 8q21, 8q24, 10p14, 11q, 15q13.3 and 18q21 variants, the risk of CRC increases with an increasing numbers of variant alleles for the six loci (OR(per allele) = 1.19; 95% CI: 1.15-1.23; P(trend) = 7.4 x 10(-24)). Using the data from our genome-wide association study of CRC, LD mapping and imputation, we were able to refine the location of the causal locus to a 60 kb region and screened for coding changes. The absence of exonic mutations in any of the transcripts (FLJ45803, LOC120376, C11orf53 and POU2AF1) mapping to this region makes the association likely to be a consequence of non-coding effects on gene expression.
Pittman
Alan M
AM
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
Webb
Emily
E
Carvajal-Carmona
Luis
L
Howarth
Kimberley
K
Di Bernardo
Maria Chiara
MC
Broderick
Peter
P
Spain
Sarah
S
Walther
Axel
A
Price
Amy
A
Sullivan
Kate
K
Twiss
Philip
P
Fielding
Sarah
S
Rowan
Andrew
A
Jaeger
Emma
E
Vijayakrishnan
Jayaram
J
Chandler
Ian
I
Penegar
Steven
S
Qureshi
Mobshra
M
Lubbe
Steven
S
Domingo
Enric
E
Kemp
Zoe
Z
Barclay
Ella
E
Wood
Wendy
W
Martin
Lynn
L
Gorman
Maggie
M
Thomas
Huw
H
Peto
Julian
J
Bishop
Timothy
T
Gray
Richard
R
Maher
Eamonn R
ER
Lucassen
Anneke
A
Kerr
David
D
Evans
Gareth R
GR
van Wezel
Tom
T
Morreau
Hans
H
Wijnen
Juul T
JT
Hopper
John L
JL
Southey
Melissa C
MC
Giles
Graham G
GG
Severi
Gianluca
G
Castellví-Bel
Sergi
S
Ruiz-Ponte
Clara
C
Carracedo
Angel
A
Castells
Antoni
A
Försti
Asta
A
Hemminki
Kari
K
Vodicka
Pavel
P
Naccarati
Alessio
A
Lipton
Lara
L
Ho
Judy W C
JW
Cheng
K K
KK
Sham
Pak C
PC
Luk
J
J
Agúndez
Jose A G
JA
Ladero
Jose M
JM
de la Hoya
Miguel
M
Caldés
Trinidad
T
Niittymäki
Iina
I
Tuupanen
Sari
S
Karhu
Auli
A
Aaltonen
Lauri A
LA
Cazier
Jean-Baptiste
JB
Tomlinson
Ian P M
IP
Houlston
Richard S
RS