Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33
Houlston RS., Cheadle J., Dobbins SE., Tenesa A., Jones AM., Howarth K., Spain SL., Broderick P., Domingo E., Farrington S., Prendergast JGD., Pittman AM., Theodoratou E., Smith CG., Olver B., Walther A., Barnetson RA., Churchman M., Jaeger EEM., Penegar S., Barclay E., Martin L., Gorman M., Mager R., Johnstone E., Midgley R., Niittymäki I., Tuupanen S., Colley J., Idziaszczyk S., Thomas HJW., Lucassen AM., Evans DGR., Maher ER., Maughan T., Dimas A., Dermitzakis E., Cazier JB., Aaltonen LA., Pharoah P., Kerr DJ., Carvajal-Carmona LG., Campbell H., Dunlop MG., Tomlinson IPM.
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. © 2010 Nature America, Inc. All rights reserved.