Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

Malcolm G Dunlop; Sara E Dobbins; Susan Mary Farrington; Angela M Jones; Claire Palles; Nicola Whiffin; Albert Tenesa; Sarah Spain; Peter Broderick; Li-Yin Ooi; Enric Domingo; Claire Smillie; Marc Henrion; Matthew Frampton; Lynn Martin; Graeme Grimes; Maggie Gorman; Colin Semple; Yusanne P Ma; Ella Barclay; James Prendergast; Jean-Baptiste Cazier; Bianca Olver; Steven Penegar; Steven Lubbe; Ian Chander; Luis G Carvajal-Carmona; Stephane Ballereau; Amy Lloyd; Jayaram Vijayakrishnan; Lina Zgaga; Igor Rudan; Evropi Theodoratou; John M Starr; Ian Deary; Iva Kirac; Dujo Kovacević; Lauri A Aaltonen; Laura Renkonen-Sinisalo; Jukka-Pekka Mecklin; Koichi Matsuda; Yusuke Nakamura; Yukinori Okada; Steven Gallinger; David J Duggan; David Conti; Polly Newcomb; John Hopper; Mark A Jenkins; Colorectal Tumour Gene Identification (CORGI) Consortium; Eamonn Maher

doi:10.1038/ng.2293

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

Malcolm G Dunlop, Sara E Dobbins, Susan Mary Farrington, Angela M Jones, Claire Palles, Nicola Whiffin, Albert Tenesa, Sarah Spain, Peter Broderick, Li-Yin Ooi, Enric Domingo, Claire Smillie, Marc Henrion, Matthew Frampton, Lynn Martin, Graeme Grimes, Maggie Gorman, Colin Semple, Yusanne P Ma, Ella BarclayJames Prendergast, Jean-Baptiste Cazier, Bianca Olver, Steven Penegar, Steven Lubbe, Ian Chander, Luis G Carvajal-Carmona, Stephane Ballereau, Amy Lloyd, Jayaram Vijayakrishnan, Lina Zgaga, Igor Rudan, Evropi Theodoratou, John M Starr, Ian Deary, Iva Kirac, Dujo Kovacević, Lauri A Aaltonen, Laura Renkonen-Sinisalo, Jukka-Pekka Mecklin, Koichi Matsuda, Yusuke Nakamura, Yukinori Okada, Steven Gallinger, David J Duggan, David Conti, Polly Newcomb, John Hopper, Mark A Jenkins, Colorectal Tumour Gene Identification (CORGI) Consortium, Eamonn Maher

Research output: Contribution to journal › Article › peer-review

177 Citations (Scopus)

Abstract

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

Original language	English
Pages (from-to)	770-6
Number of pages	7
Journal	Nature Genetics
Volume	44
Issue number	7
DOIs	https://doi.org/10.1038/ng.2293
Publication status	Published - 2012

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Dunlop, M. G., Dobbins, S. E., Farrington, S. M., Jones, A. M., Palles, C., Whiffin, N., Tenesa, A., Spain, S., Broderick, P., Ooi, L.-Y., Domingo, E., Smillie, C., Henrion, M., Frampton, M., Martin, L., Grimes, G., Gorman, M., Semple, C., Ma, Y. P., ... Maher, E. (2012). Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk. Nature Genetics, 44(7), 770-6. https://doi.org/10.1038/ng.2293

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title = "Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk",

abstract = "We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.",

author = "Dunlop, {Malcolm G} and Dobbins, {Sara E} and Farrington, {Susan Mary} and Jones, {Angela M} and Claire Palles and Nicola Whiffin and Albert Tenesa and Sarah Spain and Peter Broderick and Li-Yin Ooi and Enric Domingo and Claire Smillie and Marc Henrion and Matthew Frampton and Lynn Martin and Graeme Grimes and Maggie Gorman and Colin Semple and Ma, {Yusanne P} and Ella Barclay and James Prendergast and Jean-Baptiste Cazier and Bianca Olver and Steven Penegar and Steven Lubbe and Ian Chander and Carvajal-Carmona, {Luis G} and Stephane Ballereau and Amy Lloyd and Jayaram Vijayakrishnan and Lina Zgaga and Igor Rudan and Evropi Theodoratou and Starr, {John M} and Ian Deary and Iva Kirac and Dujo Kovacevi{\'c} and Aaltonen, {Lauri A} and Laura Renkonen-Sinisalo and Jukka-Pekka Mecklin and Koichi Matsuda and Yusuke Nakamura and Yukinori Okada and Steven Gallinger and Duggan, {David J} and David Conti and Polly Newcomb and John Hopper and Jenkins, {Mark A} and {Colorectal Tumour Gene Identification (CORGI) Consortium} and Eamonn Maher",

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doi = "10.1038/ng.2293",

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volume = "44",

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Dunlop, MG, Dobbins, SE, Farrington, SM, Jones, AM, Palles, C, Whiffin, N, Tenesa, A, Spain, S, Broderick, P, Ooi, L-Y, Domingo, E, Smillie, C, Henrion, M, Frampton, M, Martin, L, Grimes, G, Gorman, M, Semple, C, Ma, YP, Barclay, E, Prendergast, J, Cazier, J-B, Olver, B, Penegar, S, Lubbe, S, Chander, I, Carvajal-Carmona, LG, Ballereau, S, Lloyd, A, Vijayakrishnan, J, Zgaga, L, Rudan, I, Theodoratou, E, Starr, JM, Deary, I, Kirac, I, Kovacević, D, Aaltonen, LA, Renkonen-Sinisalo, L, Mecklin, J-P, Matsuda, K, Nakamura, Y, Okada, Y, Gallinger, S, Duggan, DJ, Conti, D, Newcomb, P, Hopper, J, Jenkins, MA, Colorectal Tumour Gene Identification (CORGI) Consortium & Maher, E 2012, 'Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk', Nature Genetics, vol. 44, no. 7, pp. 770-6. https://doi.org/10.1038/ng.2293

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T1 - Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

AU - Dunlop, Malcolm G

AU - Dobbins, Sara E

AU - Farrington, Susan Mary

AU - Jones, Angela M

AU - Palles, Claire

AU - Whiffin, Nicola

AU - Tenesa, Albert

AU - Spain, Sarah

AU - Broderick, Peter

AU - Ooi, Li-Yin

AU - Domingo, Enric

AU - Smillie, Claire

AU - Henrion, Marc

AU - Frampton, Matthew

AU - Martin, Lynn

AU - Grimes, Graeme

AU - Gorman, Maggie

AU - Semple, Colin

AU - Ma, Yusanne P

AU - Barclay, Ella

AU - Prendergast, James

AU - Cazier, Jean-Baptiste

AU - Olver, Bianca

AU - Penegar, Steven

AU - Lubbe, Steven

AU - Chander, Ian

AU - Carvajal-Carmona, Luis G

AU - Ballereau, Stephane

AU - Lloyd, Amy

AU - Vijayakrishnan, Jayaram

AU - Zgaga, Lina

AU - Rudan, Igor

AU - Theodoratou, Evropi

AU - Starr, John M

AU - Deary, Ian

AU - Kirac, Iva

AU - Kovacević, Dujo

AU - Aaltonen, Lauri A

AU - Renkonen-Sinisalo, Laura

AU - Mecklin, Jukka-Pekka

AU - Matsuda, Koichi

AU - Nakamura, Yusuke

AU - Okada, Yukinori

AU - Gallinger, Steven

AU - Duggan, David J

AU - Conti, David

AU - Newcomb, Polly

AU - Hopper, John

AU - Jenkins, Mark A

AU - Colorectal Tumour Gene Identification (CORGI) Consortium

AU - Maher, Eamonn

PY - 2012

Y1 - 2012

N2 - We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

AB - We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

U2 - 10.1038/ng.2293

DO - 10.1038/ng.2293

M3 - Article

C2 - 22634755

SN - 1546-1718

VL - 44

SP - 770

EP - 776

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

Abstract

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