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

A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.
A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.
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
breast-cancer, variant, prostate-cancer, familial, cancer susceptibility, trial, women, colorectal cancer, scan, colorectal-cancer, cancer, susceptibility, time, tumor, high-risk, metaanalysis, genes, predisposition, tumors, risk, families, model, chromosomes, eif3s3, gene
1061-4036
623-630
Tomlinson, I.P.M.
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Caldes, T.
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Houlston, R.S.
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Tomlinson, I.P.M.
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Webb, E.
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Qureshi, M.
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Wood, W.
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Thomas, H.
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Peto, J.
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Pharoah, P.
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Houlston, R.S.
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Tomlinson, I.P.M., Webb, E., Carvajal-Carmona, L., Broderick, P., Howarth, K., Pittman, A.M., Spain, S., Lubbe, S., Walther, A., Sullivan, K., Jaeger, E., Fielding, S., Rowan, A., Vijayakrishnan, J., Domingo, E., Chandler, I., Kemp, Z., Qureshi, M., Farrington, S.M., Tenesa, A., Prendergast, J.G.D., Barnetson, R.A., Penegar, S., Barclay, E., Wood, W., Martin, L., Gorman, M., Thomas, H., Peto, J., Bishop, D.T., Gray, R., Maher, E.R., Lucassen, A., Kerr, D., Evans, D.G.R., Schafmayer, C., Buch, S., Volzke, H., Hampe, J., Schreiber, S., John, U., Koessler, T., Pharoah, P., Van Wezel, T., Morreau, H., Wijnen, J.T., Hopper, J.L., Southey, M.C., Giles, G.G., Severi, G., Castellvi-Bel, S., Ruiz-Ponte, C., Carracedo, A., Castells, A., Forsti, A., Hemminki, K., Vodicka, P., Naccarati, A., Lipton, L., Ho, J.W.C., Cheng, K.K., Sham, P.C., Luk, J., Agundez, J.A.G., Ladero, J.M., De la Hoya, M., Caldes, T., Niittymaeki, I., Tuupanen, S., Karhu, A., Aaltonen, L., Cazier, J.B., Campbell, H., Dunlop, M.G. and Houlston, R.S. (2008) A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23. Nature Genetics, 40 (5), 623-630. (doi:10.1038/ng.111).

Record type: Article

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

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More information

Published date: 2008
Additional Information: WEB/URL: --> ISI:000255366700031; ; AU: --> Tomlinson, I. P. M., Webb, E., Carvajal-Carmona, L., Broderick, P., Howarth, K., Pittman, A. M., Spain, S., Lubbe, S., Walther, A., Sullivan, K., Jaeger, E., Fielding, S., Rowan, A., Vijayakrishnan, J., Domingo, E., Chandler, I., Kemp, Z., Qureshi, M., Farrington, S. M., Tenesa, A., Prendergast, J. G. D., Barnetson, R. A., Penegar, S., Barclay, E., Wood, W., Martin, L., Gorman, M., Thomas, H., Peto, J., Bishop, D. T., Gray, R., Maher, E. R., Lucassen, A., Kerr, D., Evans, D. G. R., Schafmayer, C., Buch, S., Volzke, H., Hampe, J., Schreiber, S., John, U., Koessler, T., Pharoah, P., van Wezel, T., Morreau, H., Wijnen, J. T., Hopper, J. L., Southey, M. C., Giles, G. G., Severi, G., Castellvi-Bel, S., Ruiz-Ponte, C., Carracedo, A., Castells, A., Forsti, A., Hemminki, K., Vodicka, P., Naccarati, A., Lipton, L., Ho, J. W. C., Cheng, K. K., Sham, P. C., Luk, J., Agundez, J. A. G., Ladero, J. M., de la Hoya, M., Caldes, T., Niittymaeki, I., Tuupanen, S., Karhu, A., Aaltonen, L., Cazier, J. B., Campbell, H., Dunlop, M. G., and Houlston, R. S.; note --> Volume => 40;
Keywords: breast-cancer, variant, prostate-cancer, familial, cancer susceptibility, trial, women, colorectal cancer, scan, colorectal-cancer, cancer, susceptibility, time, tumor, high-risk, metaanalysis, genes, predisposition, tumors, risk, families, model, chromosomes, eif3s3, gene
Organisations: Cancer Sciences, Dev Origins of Health & Disease

Identifiers

Local EPrints ID: 62957
URI: http://eprints.soton.ac.uk/id/eprint/62957
DOI: doi:10.1038/ng.111
ISSN: 1061-4036
PURE UUID: 58eff64e-4988-4a46-b9b3-a198a20338b0
ORCID for A. Lucassen: ORCID iD orcid.org/0000-0003-3324-4338

Catalogue record

Date deposited: 12 Sep 2008
Last modified: 16 Mar 2024 03:23

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Contributors

Author: I.P.M. Tomlinson
Author: E. Webb
Author: L. Carvajal-Carmona
Author: P. Broderick
Author: K. Howarth
Author: A.M. Pittman
Author: S. Spain
Author: S. Lubbe
Author: A. Walther
Author: K. Sullivan
Author: E. Jaeger
Author: S. Fielding
Author: A. Rowan
Author: J. Vijayakrishnan
Author: E. Domingo
Author: I. Chandler
Author: Z. Kemp
Author: M. Qureshi
Author: S.M. Farrington
Author: A. Tenesa
Author: J.G.D. Prendergast
Author: R.A. Barnetson
Author: S. Penegar
Author: E. Barclay
Author: W. Wood
Author: L. Martin
Author: M. Gorman
Author: H. Thomas
Author: J. Peto
Author: D.T. Bishop
Author: R. Gray
Author: E.R. Maher
Author: A. Lucassen ORCID iD
Author: D. Kerr
Author: D.G.R. Evans
Author: C. Schafmayer
Author: S. Buch
Author: H. Volzke
Author: J. Hampe
Author: S. Schreiber
Author: U. John
Author: T. Koessler
Author: P. Pharoah
Author: T. Van Wezel
Author: H. Morreau
Author: J.T. Wijnen
Author: J.L. Hopper
Author: M.C. Southey
Author: G.G. Giles
Author: G. Severi
Author: S. Castellvi-Bel
Author: C. Ruiz-Ponte
Author: A. Carracedo
Author: A. Castells
Author: A. Forsti
Author: K. Hemminki
Author: P. Vodicka
Author: A. Naccarati
Author: L. Lipton
Author: J.W.C. Ho
Author: K.K. Cheng
Author: P.C. Sham
Author: J. Luk
Author: J.A.G. Agundez
Author: J.M. Ladero
Author: M. De la Hoya
Author: T. Caldes
Author: I. Niittymaeki
Author: S. Tuupanen
Author: A. Karhu
Author: L. Aaltonen
Author: J.B. Cazier
Author: H. Campbell
Author: M.G. Dunlop
Author: R.S. Houlston

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