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.
Houlston
Richard S
RS
Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK. richard.houlston@icr.ac.uk
Cheadle
Jeremy
J
Dobbins
Sara E
SE
Tenesa
Albert
A
Jones
Angela M
AM
Howarth
Kimberley
K
Spain
Sarah L
SL
Broderick
Peter
P
Domingo
Enric
E
Farrington
Susan
S
Prendergast
James G D
JG
Pittman
Alan M
AM
Theodoratou
Evi
E
Smith
Christopher G
CG
Olver
Bianca
B
Walther
Axel
A
Barnetson
Rebecca A
RA
Churchman
Michael
M
Jaeger
Emma E M
EE
Penegar
Steven
S
Barclay
Ella
E
Martin
Lynn
L
Gorman
Maggie
M
Mager
Rachel
R
Johnstone
Elaine
E
Midgley
Rachel
R
Niittymäki
Iina
I
Tuupanen
Sari
S
Colley
James
J
Idziaszczyk
Shelley
S
Thomas
Huw J W
HJ
Lucassen
Anneke M
AM
Evans
D Gareth R
DG
Maher
Eamonn R
ER
Maughan
Timothy
T
Dimas
Antigone
A
Dermitzakis
Emmanouil
E
Cazier
Jean-Baptiste
JB
Aaltonen
Lauri A
LA
Pharoah
Paul
P
Kerr
David J
DJ
Carvajal-Carmona
Luis G
LG
Campbell
Harry
H
Dunlop
Malcolm G
MG
Tomlinson
Ian P M
IP
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