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 Jürgen, Schreiber Stefan, Völzke 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 Steven, Campbell Harry, Dunlop Malcolm G
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Edinburgh EH4 2XU, UK.
Nat Genet. 2008 May;40(5):631-7. doi: 10.1038/ng.133. Epub 2008 Mar 30.
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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