Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33

Houlston, R.S., Cheadle, J., Dobbins, S.E., Tenesa, A., Jones, A.M., Howarth, K., Spain, S.L., Broderick, P., Domingo, E., Farrington, S., Prendergast, J.G., Pittman, A.M., Theodoratou, E., Smith, C.G., Olver, B., Walther, A., Barnetson, R.A., Churchman, M., Jaeger, E.E., Pendegar, S., Barclay, E., Martin, L., Gorman, M., Mager, R., Johnstone, E., Midgley, R., Niittymaki, I., Tuupanen, S., Colley, J., Idziaszczyk, S., Thomas, H.J., Lucassen, Anneke, Evans, D.G., Maher, R.E., Maughan, T., Dimas, A., Dermitzakis, E., Cazier, J.B., Aaltonen, L.A., Pharoah, P., Kerr, D.J., Carvajal-Carmona, L.G., Campbell, H., Dunlop, M.G. and Tomlinson, I.P. (2010) Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33. Nature Genetics, 42 (11), 973-977. (doi:10.1038/ng.670).

Abstract

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.

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Contributors

Author: Anneke Lucassen

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