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

Research output: Contribution to journalArticle

  • M. E. Porteous
  • M. Walker
  • N. Haq
  • R. Cetnarskyj
  • N. Cartwright
  • A. J. Clark
  • T. Koessler
  • P. D. Pharoah
  • S. Buch
  • C. Schafmayer
  • J. Tepel
  • S. Schreiber
  • H. Volzke
  • C. O. Schmidt
  • J. Hampe
  • J. Chang-Claude
  • M. Hoffmeister
  • H. Brenner
  • S. Wilkening
  • F. Canzian
  • G. Capella
  • V. Moreno
  • I. P. Tomlinson
  • Z. Kemp
  • K. Howarth
  • L. Carvajal-Carmona
  • E. Webb
  • P. Broderick
  • J. Vijayakrishnan
  • R. S. Houlston
  • G. Rennert
  • D. Ballinger
  • L. Rozek
  • S. B. Gruber
  • K. Matsuda
  • T. Kidokoro
  • Y. Nakamura
  • B. W. Zanke
  • C. M. Greenwood
  • J. Rangrej
  • R. Kustra
  • A. Montpetit
  • T. J. Hudson
  • S. Gallinger

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    Rights statement: Published in final edited form as: Nat Genet. 2008 May ; 40(5): 631–637. doi:10.1038/ng.133.

    Accepted author manuscript, 184 KB, PDF-document

http://www.nature.com/ng/journal/v40/n5/full/ng.133.html
Original languageEnglish
Pages (from-to)631-7
Number of pages7
JournalNature Genetics
Volume40
Issue number5
DOIs
StatePublished - May 2008

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=8.6x10(-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.

    Research areas

  • *Acoustics, Albumins, Contrast Media/*chemistry, Equipment Design, *Microbubbles, Phantoms, Imaging, Polyesters, Pressure, Signal Processing, Computer-Assisted

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