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

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. Farrington; Albert Tenesa; James G.D. 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; Graham G. Giles; Gianluca Severi; Sergi Castellví-Bel; Clara Ruiz-Ponte; Angel Carracedo; Antoni Castells; Asta Försti; Kari Hemminki; Pavel Vodicka; Alessio Naccarati; Lara Lipton; Judy W.C. Ho; K. K. Cheng; Pak C. Sham; J. Luk; Jose A.G. Agúndez; Jose M. Ladero; Miguel De La Hoya; Trinidad Caldés; Iina Niittymäki; Sari Tuupanen; Auli Karhu; Lauri Aaltonen; Jean Baptiste Cazier; Harry Campbell; Malcolm G. Dunlop; Richard S. Houlston

doi:10.1038/ng.111

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

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. Farrington, Albert TenesaJames G.D. 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, Graham G. Giles, Gianluca Severi, Sergi Castellví-Bel, Clara Ruiz-Ponte, Angel Carracedo, Antoni Castells, Asta Försti, Kari Hemminki, Pavel Vodicka, Alessio Naccarati, Lara Lipton, Judy W.C. Ho, K. K. Cheng, Pak C. Sham, J. Luk, Jose A.G. Agúndez, Jose M. Ladero, Miguel De La Hoya, Trinidad Caldés, Iina Niittymäki, Sari Tuupanen, Auli Karhu, Lauri Aaltonen, Jean Baptiste Cazier, Harry Campbell, Malcolm G. Dunlop, Richard S. Houlston

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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 × 10 ^-13 overall; P = 6.9 × 10^-12 replication), and rs16892766, at 8q23.3 (P = 3.3 × 10^-18 overall; P = 9.6 × 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 language	English
Pages (from-to)	623-630
Number of pages	8
Journal	Nature Genetics
Volume	40
Issue number	5
DOIs	https://doi.org/10.1038/ng.111
Publication status	Published - 1 May 2008
Externally published	Yes

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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., ... Houlston, R. S. (2008). A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nature Genetics, 40(5), 623-630. https://doi.org/10.1038/ng.111

@article{422c81712b4d422b9029abfef4f938af,

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

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 × 10 -13 overall; P = 6.9 × 10-12 replication), and rs16892766, at 8q23.3 (P = 3.3 × 10-18 overall; P = 9.6 × 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.",

author = "Tomlinson, {Ian P.M.} and Emily Webb and Luis Carvajal-Carmona and Peter Broderick and Kimberley Howarth and Pittman, {Alan M.} and Sarah Spain and Steven Lubbe and Axel Walther and Kate Sullivan and Emma Jaeger and Sarah Fielding and Andrew Rowan and Jayaram Vijayakrishnan and Enric Domingo and Ian Chandler and Zoe Kemp and Mobshra Qureshi and Farrington, {Susan M.} and Albert Tenesa and Prendergast, {James G.D.} and Barnetson, {Rebecca A.} and Steven Penegar and Ella Barclay and Wendy Wood and Lynn Martin and Maggie Gorman and Huw Thomas and Julian Peto and Bishop, {D. Timothy} and Richard Gray and Maher, {Eamonn R.} and Anneke Lucassen and David Kerr and Evans, {D. Gareth R.} and Clemens Schafmayer and Stephan Buch and Henry V{\"o}lzke and Jochen Hampe and Stefan Schreiber and Ulrich John and Thibaud Koessler and Paul Pharoah and {Van Wezel}, Tom and Hans Morreau and Wijnen, {Juul T.} and Hopper, {John L.} and Southey, {Melissa C.} and Giles, {Graham G.} and Gianluca Severi and Sergi Castellv{\'i}-Bel and Clara Ruiz-Ponte and Angel Carracedo and Antoni Castells and Asta F{\"o}rsti and Kari Hemminki and Pavel Vodicka and Alessio Naccarati and Lara Lipton and Ho, {Judy W.C.} and Cheng, {K. K.} and Sham, {Pak C.} and J. Luk and Ag{\'u}ndez, {Jose A.G.} and Ladero, {Jose M.} and {De La Hoya}, Miguel and Trinidad Cald{\'e}s and Iina Niittym{\"a}ki and Sari Tuupanen and Auli Karhu and Lauri Aaltonen and Cazier, {Jean Baptiste} and Harry Campbell and Dunlop, {Malcolm G.} and Houlston, {Richard S.}",

year = "2008",

month = may,

day = "1",

doi = "10.1038/ng.111",

language = "English",

volume = "40",

pages = "623--630",

journal = "Nature Genetics",

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Tomlinson, IPM, Webb, E, Carvajal-Carmona, L, Broderick, P, Howarth, K, Pittman, AM, 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, SM, Tenesa, A, Prendergast, JGD, Barnetson, RA, Penegar, S, Barclay, E, Wood, W, Martin, L, Gorman, M, Thomas, H, Peto, J, Bishop, DT, Gray, R, Maher, ER, Lucassen, A, Kerr, D, Evans, DGR, Schafmayer, C, Buch, S, Völzke, H, Hampe, J, Schreiber, S, John, U, Koessler, T, Pharoah, P, Van Wezel, T, Morreau, H, Wijnen, JT, Hopper, JL, Southey, MC, Giles, GG, Severi, G, Castellví-Bel, S, Ruiz-Ponte, C, Carracedo, A, Castells, A, Försti, A, Hemminki, K, Vodicka, P, Naccarati, A, Lipton, L, Ho, JWC, Cheng, KK, Sham, PC, Luk, J, Agúndez, JAG, Ladero, JM, De La Hoya, M, Caldés, T, Niittymäki, I, Tuupanen, S, Karhu, A, Aaltonen, L, Cazier, JB, Campbell, H, Dunlop, MG & Houlston, RS 2008, 'A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3', Nature Genetics, vol. 40, no. 5, pp. 623-630. https://doi.org/10.1038/ng.111

TY - JOUR

T1 - A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3

AU - Tomlinson, Ian P.M.

AU - Webb, Emily

AU - Carvajal-Carmona, Luis

AU - Broderick, Peter

AU - Howarth, Kimberley

AU - Pittman, Alan M.

AU - Spain, Sarah

AU - Lubbe, Steven

AU - Walther, Axel

AU - Sullivan, Kate

AU - Jaeger, Emma

AU - Fielding, Sarah

AU - Rowan, Andrew

AU - Vijayakrishnan, Jayaram

AU - Domingo, Enric

AU - Chandler, Ian

AU - Kemp, Zoe

AU - Qureshi, Mobshra

AU - Farrington, Susan M.

AU - Tenesa, Albert

AU - Prendergast, James G.D.

AU - Barnetson, Rebecca A.

AU - Penegar, Steven

AU - Barclay, Ella

AU - Wood, Wendy

AU - Martin, Lynn

AU - Gorman, Maggie

AU - Thomas, Huw

AU - Peto, Julian

AU - Bishop, D. Timothy

AU - Gray, Richard

AU - Maher, Eamonn R.

AU - Lucassen, Anneke

AU - Kerr, David

AU - Evans, D. Gareth R.

AU - Schafmayer, Clemens

AU - Buch, Stephan

AU - Völzke, Henry

AU - Hampe, Jochen

AU - Schreiber, Stefan

AU - John, Ulrich

AU - Koessler, Thibaud

AU - Pharoah, Paul

AU - Van Wezel, Tom

AU - Morreau, Hans

AU - Wijnen, Juul T.

AU - Hopper, John L.

AU - Southey, Melissa C.

AU - Giles, Graham G.

AU - Severi, Gianluca

AU - Castellví-Bel, Sergi

AU - Ruiz-Ponte, Clara

AU - Carracedo, Angel

AU - Castells, Antoni

AU - Försti, Asta

AU - Hemminki, Kari

AU - Vodicka, Pavel

AU - Naccarati, Alessio

AU - Lipton, Lara

AU - Ho, Judy W.C.

AU - Cheng, K. K.

AU - Sham, Pak C.

AU - Luk, J.

AU - Agúndez, Jose A.G.

AU - Ladero, Jose M.

AU - De La Hoya, Miguel

AU - Caldés, Trinidad

AU - Niittymäki, Iina

AU - Tuupanen, Sari

AU - Karhu, Auli

AU - Aaltonen, Lauri

AU - Cazier, Jean Baptiste

AU - Campbell, Harry

AU - Dunlop, Malcolm G.

AU - Houlston, Richard S.

PY - 2008/5/1

Y1 - 2008/5/1

N2 - 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 × 10 -13 overall; P = 6.9 × 10-12 replication), and rs16892766, at 8q23.3 (P = 3.3 × 10-18 overall; P = 9.6 × 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.

AB - 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 × 10 -13 overall; P = 6.9 × 10-12 replication), and rs16892766, at 8q23.3 (P = 3.3 × 10-18 overall; P = 9.6 × 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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U2 - 10.1038/ng.111

DO - 10.1038/ng.111

M3 - Article

C2 - 18372905

AN - SCOPUS:42649136554

SN - 1061-4036

VL - 40

SP - 623

EP - 630

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

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