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 Tepel & 37 others Stefan 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 journalArticle

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

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Genome-Wide Association Study
Colorectal Neoplasms
Single Nucleotide Polymorphism
Rectal Neoplasms
Colonic Neoplasms
Population
Joints
Alleles

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Tenesa, A., Farrington, S. M., Prendergast, J. G. D., Porteous, M. E., Walker, M., Haq, N., ... Dunlop, M. G. (2008). Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nature Genetics, 40(5), 631-637. https://doi.org/10.1038/ng.133

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

In: Nature Genetics, Vol. 40, No. 5, 05.2008, p. 631-637.

Research output: Contribution to journalArticle

Tenesa, A, Farrington, SM, Prendergast, JGD, Porteous, ME, Walker, M, Haq, N, Barnetson, RA, Theodoratou, E, Cetnarskyj, R, Cartwright, N, Semple, C, Clark, AJ, Reid, FJL, Smith, LA, Kavoussanakis, K, Koessler, T, Pharoah, PDP, Buch, S, Schafmayer, C, Tepel, J, Schreiber, S, Völzke, H, Schmidt, CO, Hampe, J, Chang-Claude, J, Hoffmeister, M, Brenner, H, Wilkening, S, Canzian, F, Capella, G, Moreno, V, Deary, IJ, Starr, JM, Tomlinson, IPM, Kemp, Z, Howarth, K, Carvajal-Carmona, L, Webb, E, Broderick, P, Vijayakrishnan, J, Houlston, RS, Rennert, G, Ballinger, D, Rozek, L, Gruber, SB, Matsuda, K, Kidokoro, T, Nakamura, Y, Zanke, BW, Greenwood, CMT, Rangrej, J, Kustra, R, Montpetit, A, Hudson, TJ, Gallinger, S, Campbell, H & Dunlop, MG 2008, 'Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21', Nature Genetics, vol. 40, no. 5, pp. 631-637. https://doi.org/10.1038/ng.133
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. / Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. In: Nature Genetics. 2008 ; Vol. 40, No. 5. pp. 631-637.
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title = "Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21",
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.",
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T1 - Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21

AU - Tenesa, Albert

AU - Farrington, Susan M.

AU - Prendergast, James G D

AU - Porteous, Mary E.

AU - Walker, Marion

AU - Haq, Naila

AU - Barnetson, Rebecca A.

AU - Theodoratou, Evropi

AU - Cetnarskyj, Roseanne

AU - Cartwright, Nicola

AU - Semple, Colin

AU - Clark, Andrew J.

AU - Reid, Fiona J L

AU - Smith, Lorna A.

AU - Kavoussanakis, Kostas

AU - Koessler, Thibaud

AU - Pharoah, Paul D P

AU - Buch, Stephan

AU - Schafmayer, Clemens

AU - Tepel, Jürgen

AU - Schreiber, Stefan

AU - Völzke, Henry

AU - Schmidt, Carsten O.

AU - Hampe, Jochen

AU - Chang-Claude, Jenny

AU - Hoffmeister, Michael

AU - Brenner, Hermann

AU - Wilkening, Stefan

AU - Canzian, Federico

AU - Capella, Gabriel

AU - Moreno, Victor

AU - Deary, Ian J.

AU - Starr, John M.

AU - Tomlinson, Ian P M

AU - Kemp, Zoe

AU - Howarth, Kimberley

AU - Carvajal-Carmona, Luis

AU - Webb, Emily

AU - Broderick, Peter

AU - Vijayakrishnan, Jayaram

AU - Houlston, Richard S.

AU - Rennert, Gad

AU - Ballinger, Dennis

AU - Rozek, Laura

AU - Gruber, Stephen B.

AU - Matsuda, Koichi

AU - Kidokoro, Tomohide

AU - Nakamura, Yusuke

AU - Zanke, Brent W.

AU - Greenwood, Celia M T

AU - Rangrej, Jagadish

AU - Kustra, Rafal

AU - Montpetit, Alexandre

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AU - Gallinger, Steven

AU - Campbell, Harry

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