A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3

CORGI Consortium, Ian P M Tomlinson, Emily Webb, Luis Carvajal-Carmona, Peter Broderick, Kimberley Howarth, Alan M Pittman, Sarah Spain, Steven Lubbe, Axel Walther, Kate Sullivan, Emma Jaeger, Sarah Fielding, Andrew Rowan, Jayaram Vijayakrishnan, Enric Domingo, Ian Chandler, Zoe Kemp, Mobshra Qureshi, Susan M FarringtonAlbert Tenesa, James Prendergast, Rebecca A Barnetson, Steven Penegar, Ella Barclay, Wendy Wood, Lynn Martin, Maggie Gorman, Huw Thomas, Julian Peto, D Timothy Bishop, Richard Gray, Eamonn R Maher, Anneke Lucassen, David Kerr, D Gareth R Evans, Clemens Schafmayer, Stephan Buch, Henry Völzke, Jochen Hampe, Stefan Schreiber, Ulrich John, Thibaud Koessler, Paul Pharoah, Tom van Wezel, Hans Morreau, Juul T Wijnen, John L Hopper, Melissa C Southey, Harry Campbell, Malcolm G Dunlop

Research output: Contribution to journalArticlepeer-review

Abstract

To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P <10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 x 10(-13) overall; P = 6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P = 3.3 x 10(-18) overall; P = 9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.
Original languageEnglish
Pages (from-to)623-630
Number of pages8
JournalNature Genetics
Volume40
Issue number5
DOIs
Publication statusPublished - May 2008

Keywords

  • Adult
  • Aged
  • Alleles
  • Chromosomes, Human, Pair 10
  • Chromosomes, Human, Pair 8
  • Colorectal Neoplasms
  • Eukaryotic Initiation Factor-3
  • Female
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Genome, Human
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Polymorphism, Single Nucleotide

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