Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33.
Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10⁻¹⁰ and rs6687758, OR = 1.09, P = 2.27 × 10⁻⁹, 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10⁻⁸), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10⁻¹⁰ and rs7136702, OR = 1.06, P = 4.02 × 10⁻⁸) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10⁻¹⁰). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.
Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK. richard.houlston@icr.ac.uk
Richard S
RS
Houlston
Jeremy
J
Cheadle
Sara E
SE
Dobbins
Albert
A
Tenesa
Angela M
AM
Jones
Kimberley
K
Howarth
Sarah L
SL
Spain
Peter
P
Broderick
Enric
E
Domingo
Susan
S
Farrington
James G D
JG
Prendergast
Alan M
AM
Pittman
Evi
E
Theodoratou
Christopher G
CG
Smith
Bianca
B
Olver
Axel
A
Walther
Rebecca A
RA
Barnetson
Michael
M
Churchman
Emma E M
EE
Jaeger
Steven
S
Penegar
Ella
E
Barclay
Lynn
L
Martin
Maggie
M
Gorman
Rachel
R
Mager
Elaine
E
Johnstone
Rachel
R
Midgley
Iina
I
Niittymäki
Sari
S
Tuupanen
James
J
Colley
Shelley
S
Idziaszczyk
Huw J W
HJ
Thomas
Anneke M
AM
Lucassen
D Gareth R
DG
Evans
Eamonn R
ER
Maher
Timothy
T
Maughan
Antigone
A
Dimas
Emmanouil
E
Dermitzakis
Jean-Baptiste
JB
Cazier
Lauri A
LA
Aaltonen
Paul
P
Pharoah
David J
DJ
Kerr
Luis G
LG
Carvajal-Carmona
Harry
H
Campbell
Malcolm G
MG
Dunlop
Ian P M
IP
Tomlinson
D002874:Chromosome Mapping / Q000379:methods; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment