Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21

Tenesa, Albert; Farrington, Susan M; Prendergast, James G D; Porteous, Mary E; Walker, Marion; Haq, Naila; Barnetson, Rebecca A; Theodoratou, Evropi; Cetnarskyj, Roseanne; Cartwright, Nicola; Semple, Colin; Clark, Andrew J; Reid, Fiona J L; Smith, Lorna A; Kavoussanakis, Kostas; Koessler, Thibaud; Pharoah, Paul D P; Buch, Stephan; Schafmayer, Clemens; Tepel, J?rgen; Schreiber, Stefan; V?lzke, Henry; Schmidt, Carsten O; Hampe, Jochen; Chang-Claude, Jenny; Hoffmeister, Michael; Brenner, Hermann; Wilkening, Stefan; Canzian, Federico; Capella, Gabriel; Moreno, Victor; Deary, Ian J; Starr, John M; Tomlinson, Ian P M; Kemp, Zoe; Howarth, Kimberley; Carvajal-Carmona, Luis; Webb, Emily; Broderick, Peter; Vijayakrishnan, Jayaram; Houlston, Richard S; Rennert, Gad; Ballinger, Dennis; Rozek, Laura; Gruber, Stephen B; Matsuda, Koichi; Kidokoro, Tomohide; Nakamura, Yusuke; Zanke, Brent W; Greenwood, Celia M T; Rangrej, Jagadish; Kustra, Rafal; Montpetit, Alexandre; Hudson, Thomas J; Gallinger, Stev...

Abstract

In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 10-10), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 10-26) and 18q21 (rs4939827; OR = 1.2; P = 7.8 10-28). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75–3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.

Citation

Tenesa, A., Farrington, S. M., Prendergast, J. G. D., Porteous, M. E., Walker, M., Haq, N., Barnetson, R. A., Theodoratou, E., Cetnarskyj, R., Cartwright, N., Semple, C., Clark, A. J., Reid, F. J. L., Smith, L. A., Kavoussanakis, K., Koessler, T., Pharoah, P. D. P., Buch, S., Schafmayer, C., Tepel, J., …Dunlop, M. G. (2008). Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nature Genetics, 40(5), 631-637. https://doi.org/10.1038/ng.133

• Journal Article Type: Article
• Publication Date: 2008-05
• Deposit Date: Mar 13, 2014
• Print ISSN: 1061-4036
• Electronic ISSN: 1546-1718
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 40
• Issue: 5
• Pages: 631-637
• DOI: https://doi.org/10.1038/ng.133
• Keywords: Colorectal cancer; genetic variation; CRC etiology
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/6616
• Publisher URL: http://dx.doi.org/10.1038/ng.133