A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3.
;
Luis Carvajal-Carmona;
Peter Broderick;
Kimberley Howarth;
Alan M Pittman;
Sarah Spain;
Steven Lubbe;
Axel Walther;
Kate Sullivan;
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Emma Jaeger;
Sarah Fielding;
Andrew Rowan;
Jayaram Vijayakrishnan;
Enric Domingo;
Ian Chandler;
Zoe Kemp;
Mobshra Qureshi;
Susan M Farrington;
Albert Tenesa;
James GD Prendergast;
Rebecca A Barnetson;
Steven Penegar;
Ella Barclay;
Wendy Wood;
Lynn Martin;
Maggie Gorman;
Huw Thomas;
Julian Peto ;
D Timothy Bishop;
Richard Gray;
Eamonn R Maher;
Anneke Lucassen;
David Kerr;
D Gareth R Evans;
CORGI Consortium;
Clemens Schafmayer;
Stephan Buch;
Henry Völzke;
Jochen Hampe;
Stefan Schreiber;
Ulrich John;
Thibaud Koessler;
Paul Pharoah;
Tom van Wezel;
Hans Morreau;
Juul T Wijnen;
John L Hopper;
Melissa C Southey;
Graham G Giles;
Gianluca Severi;
Sergi Castellví-Bel;
Clara Ruiz-Ponte;
Angel Carracedo;
Antoni Castells;
EPICOLON Consortium;
Asta Försti;
Kari Hemminki;
Pavel Vodicka;
Alessio Naccarati;
Lara Lipton;
Judy WC Ho;
KK Cheng;
Pak C Sham;
J Luk;
Jose AG Agúndez;
Jose M Ladero;
Miguel de la Hoya;
Trinidad Caldés;
Iina Niittymäki;
Sari Tuupanen;
Auli Karhu;
Lauri Aaltonen;
Jean-Baptiste Cazier;
Harry Campbell;
Malcolm G Dunlop;
Richard S Houlston;
(2008)
A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3.
Nature genetics, 40 (5).
pp. 623-630.
ISSN 1061-4036
DOI: 10.1038/ng.111
To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 x 10(-13) overall; P = 6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P = 3.3 x 10(-18) overall; P = 9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.