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. 2008 May;40(5):631-7.
doi: 10.1038/ng.133. Epub 2008 Mar 30.

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

Albert Tenesa  1 , Susan M Farrington, James G D Prendergast, Mary E Porteous, Marion Walker, Naila Haq, Rebecca A Barnetson, Evropi Theodoratou, Roseanne Cetnarskyj, Nicola Cartwright, Colin Semple, Andrew J Clark, Fiona J L Reid, Lorna A Smith, Kostas Kavoussanakis, Thibaud Koessler, Paul D P Pharoah, Stephan Buch, Clemens Schafmayer, Jürgen Tepel, Stefan Schreiber, Henry Völzke, Carsten O Schmidt, Jochen Hampe, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Stefan Wilkening, Federico Canzian, Gabriel Capella, Victor Moreno, Ian J Deary, John M Starr, Ian P M Tomlinson, Zoe Kemp, Kimberley Howarth, Luis Carvajal-Carmona, Emily Webb, Peter Broderick, Jayaram Vijayakrishnan, Richard S Houlston, Gad Rennert, Dennis Ballinger, Laura Rozek, Stephen B Gruber, Koichi Matsuda, Tomohide Kidokoro, Yusuke Nakamura, Brent W Zanke, Celia M T Greenwood, Jagadish Rangrej, Rafal Kustra, Alexandre Montpetit, Thomas J Hudson, Steven Gallinger, Harry Campbell, Malcolm G Dunlop
Affiliations

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

Albert Tenesa et al. Nat Genet. 2008 May.

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 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 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.

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Figures

Figure 1
Figure 1
Fine mapping of the 8q24 and 18q23 (SMAD7) loci. Graphs show -log10P against distance. Black dots correspond to the analysis of data generated from phase 1 and 2 individuals. Red dots are from the analysis of data from phase 2 individuals. rslDS are provided for the SNPs with peak evidence for association. These fine mapping data are further informed by results shown in Supplementary Figure 7 from IMPUTE and SNPTEST analysis of the loci on chromosomes 8q, 18q and 11q.
Figure 2
Figure 2
Forest plot of effect size and direction for each of the three SNPs associated with CRC (rs7014346, rs4939827 and rs3802842). Symbol size indicates the weight of the study in the fixed effect model (the larger the symbol, the greater the weight), as in the output from the program R. rs3802842 was stratified by ethnic group, because most of the heterogeneity observed was due to differences between GWAS data from the Scottish and the Japanese populations.
See this image and copyright information in PMC

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