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

478 Scopus citations

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 (US)
Pages (from-to)631-637
Number of pages7
JournalNature Genetics
Volume40
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Fingerprint

Dive into the research topics of 'Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21'. Together they form a unique fingerprint.

Cite this