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

Albert Tenesa, 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 TepelStefan 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

    Research output: Contribution to journalArticlepeer-review

    468 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)631-637
    Number of pages7
    JournalNature Genetics
    Volume40
    Issue number5
    Early online date30 Mar 2008
    DOIs
    Publication statusPublished - May 2008

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