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

被引：471

作者：

Tenesa, Albert ^{[1
,2
]}

Farrington, Susan M. ^{[1
,2
]}

Prendergast, James G. D. ^{[1
,2
]}

Porteous, Mary E. ^{[3
]}

Walker, Marion ^{[1
,2
]}

Haq, Naila ^{[1
,2
]}

Barnetson, Rebecca A. ^{[1
,2
]}

Theodoratou, Evropi ^{[1
,2
,4
]}

Cetnarskyj, Roseanne ^{[3
]}

Cartwright, Nicola ^{[1
,2
]}

Semple, Colin ^{[1
,2
]}

Clark, Andrew J. ^{[1
,2
]}

Reid, Fiona J. L. ^{[5
]}

Smith, Lorna A. ^{[5
]}

Kavoussanakis, Kostas ^{[5
]}

Koessler, Thibaud ^{[6
]}

Pharoah, Paul D. P. ^{[6
]}

Buch, Stephan ^{[7
,8
]}

Schafmayer, Clemens ^{[8
,9
]}

Tepel, Juergen ^{[7
,9
]}

Schreiber, Stefan ^{[8
,10
]}

Voelzke, Henry ^{[11
]}

Schmidt, Carsten O. ^{[11
]}

Hampe, Jochen ^{[7
]}

Chang-Claude, Jenny ^{[12
]}

Hoffmeister, Michael ^{[13
]}

Brenner, Hermann ^{[13
]}

Wilkening, Stefan ^{[14
]}

Canzian, Federico ^{[14
]}

Capella, Gabriel ^{[15
]}

Moreno, Victor ^{[16
,17
]}

Deary, Ian J. ^{[18
]}

Starr, John M. ^{[19
]}

Tomlinson, Ian P. M. ^{[20
]}

Kemp, Zoe ^{[20
]}

Howarth, Kimberley ^{[20
]}

Carvajal-Carmona, Luis ^{[20
]}

Webb, Emily ^{[21
]}

Broderick, Peter ^{[21
]}

Vijayakrishnan, Jayaram ^{[21
]}

Houlston, Richard S. ^{[21
]}

Rennert, Gad ^{[22
]}

Ballinger, Dennis ^{[23
,24
,25
]}

Rozek, Laura ^{[26
,27
]}

Gruber, Stephen B. ^{[26
,27
]}

Matsuda, Koichi ^{[28
]}

Kidokoro, Tomohide ^{[28
]}

Nakamura, Yusuke ^{[28
]}

Zanke, Brent W. ^{[29
,31
]}

Greenwood, Celia M. T. ^{[29
,32
,33
]}

机构：

[1] Univ Edinburgh, Colon Canc Genet Grp, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland

[2] MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[3] Western Gen Hosp, Dept Clin Genet, Edinburgh EH4 2XU, Midlothian, Scotland

[4] Univ Edinburgh, Edinburgh EH8 9AG, Midlothian, Scotland

[5] Univ Edinburgh, Edinburgh Parallel Comp Ctr, Edinburgh EH9 3JZ, Midlothian, Scotland

[6] Univ Cambridge, Canc Res UK Labs, Dept Oncol, Cambridge CB1 8RN, England

[7] Univ Hosp Schleswig Holstein, Dept Gen Internal Med, D-24105 Kiel, Germany

[8] Univ Hosp Schleswig Holstein, POPGEN Biobank, D-24105 Kiel, Germany

[9] Univ Hosp Schleswig Holstein, Dept Gen & Thorac Surg, D-24105 Kiel, Germany

[10] Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, D-24105 Kiel, Germany

[11] Univ Hosp Greifswald, Inst Community Med, D-17487 Greifswald, Germany

[12] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany

[13] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany

[14] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany

[15] IDIBELL Catalan Inst Oncol, Translat Res Lab, Barcelona 08907, Spain

[16] IDIBELL Catalan Inst Oncol, Bioinformat Unit, Barcelona 08907, Spain

[17] Univ Barcelona, Barcelona 08907, Spain

[18] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland

[19] Univ Edinburgh, Royal Victoria Hosp, Edinburgh EH4 2DN, Midlothian, Scotland

[20] Canc Res UK London Res Inst, Mol & Populat Genet Lab, London WC2A 3PX, England

[21] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England

[22] Technion x2013 Israel Inst Technol, CHS Natl Canc Control Ctr, Haifa, Israel

[23] Technion x2013 Israel Inst Technol, Dept Community Med & Epidemiol, Carmel Med Ctr, Haifa, Israel

[24] Technion x2013 Israel Inst Technol, B Rappaport Fac Med, Haifa, Israel

[25] Perlegen Sci, Mountain View, CA 94043 USA

[26] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA

[27] Univ Michigan, Sch Med, Dept Epidemiol & Human Genet, Ann Arbor, MI 48109 USA

[28] Univ Tokyo, Mol Med Lab, Ctr Human Genome, Inst Med Sci, Tokyo 1088639, Japan

[29] Canc Care Ontario, Toronto, ON M5G 1L7, Canada

[30] Ontario Inst Canc Res, Toronto, ON M5G 1L7, Canada

[31] Univ Ottawa, Fac Med, Div Hematol, Ottawa, ON K1H 8L6, Canada

[32] Hosp Sick Children, Toronto, ON M5G 1L7, Canada

[33] Univ Toronto, Dept Publ Hlth Sci, Toronto, ON M57 3M7, Canada

[34] McGill Univ, Montreal, PQ H3G 1A4, Canada

[35] Genome Quebec Innovat Ctr, Montreal, PQ H3G 1A4, Canada

[36] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[37] Univ Toronto, Toronto, ON M5G 1X5, Canada

来源：

NATURE GENETICS | 2008年 / 40卷 / 05期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/ng.133

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：631 / 637

页数：7

共 50 条

[11] Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24
Julius Gudmundsson
Patrick Sulem
Andrei Manolescu
Laufey T Amundadottir
Daniel Gudbjartsson
Agnar Helgason
Thorunn Rafnar
Jon T Bergthorsson
Bjarni A Agnarsson
Adam Baker
Asgeir Sigurdsson
Kristrun R Benediktsdottir
Margret Jakobsdottir
Jianfeng Xu
Thorarinn Blondal
Jelena Kostic
Jielin Sun
Shyamali Ghosh
Simon N Stacey
Magali Mouy
Jona Saemundsdottir
Valgerdur M Backman
Kristleifur Kristjansson
Alejandro Tres
Alan W Partin
Marjo T Albers-Akkers
Javier Godino-Ivan Marcos
Patrick C Walsh
Dorine W Swinkels
Sebastian Navarrete
Sarah D Isaacs
Katja K Aben
Theresa Graif
John Cashy
Manuel Ruiz-Echarri
Kathleen E Wiley
Brian K Suarez
J Alfred Witjes
Mike Frigge
Carole Ober
Eirikur Jonsson
Gudmundur V Einarsson
Jose I Mayordomo
Lambertus A Kiemeney
William B Isaacs
William J Catalona
Rosa B Barkardottir
Jeffrey R Gulcher
Unnur Thorsteinsdottir
Augustine Kong
Nature Genetics, 2007, 39 : 631 - 637
[12] Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24
Gudmundsson, Julius
Sulem, Patrick
Manolescu, Andrei
Amundadottir, Laufey T.
Gudbjartsson, Daniel
Helgason, Agnar
Rafnar, Thorunn
Bergthorsson, Jon T.
Agnarsson, Bjarni A.
Baker, Adam
Sigurdsson, Asgeir
Benediktsdottir, Kristrun R.
Jakobsdottir, Margret
Xu, Jianfeng
Blondal, Thorarinn
Kostic, Jelena
Sun, Jielin
Ghosh, Shyamali
Stacey, Simon N.
Mouy, Magali
Saemundsdottir, Jona
Backman, Valgerdur M.
Kristjansson, Kristleifur
Tres, Alejandro
Partin, Alan W.
Albers-Akkers, Marjo T.
Marcos, Javier Godino-Ivan
Walsh, Patrick C.
Swinkels, Dorine W.
Navarrete, Sebastian
Isaacs, Sarah D.
Aben, Katja K.
Graif, Theresa
Cashy, John
Ruiz-Echarri, Manuel
Wiley, Kathleen E.
Suarez, Brian K.
Witjes, J. Alfred
Frigge, Mike
Ober, Carole
Jonsson, Eirikur
Einarsson, Gudmundur V.
Mayordomo, Jose I.
Kiemeney, Lambertus A.
Isaacs, William B.
Catalona, William J.
Barkardottir, Rosa B.
Gulcher, Jeffrey R.
Thorsteinsdottir, Unnur
Kong, Augustine
NATURE GENETICS, 2007, 39 (05) : 631 - 637
[13] Association between an 8q24 locus and the risk of colorectal cancer in Japanese
Keitaro Matsuo
Takeshi Suzuki
Hidemi Ito
Satoyo Hosono
Takakazu Kawase
Miki Watanabe
Kohei Shitara
Koji Komori
Yukihide Kanemitsu
Takashi Hirai
Yasushi Yatabe
Hideo Tanaka
Kazuo Tajima
BMC Cancer, 9
[14] Association between an 8q24 locus and the risk of colorectal cancer in Japanese
Matsuo, Keitaro
Suzuki, Takeshi
Ito, Hidemi
Hosono, Satoyo
Kawase, Takakazu
Watanabe, Miki
Shitara, Kohei
Komori, Koji
Kanemitsu, Yukihide
Hirai, Takashi
Yatabe, Yasushi
Tanaka, Hideo
Tajima, Kazuo
BMC CANCER, 2009, 9
[15] A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21
Ian Tomlinson
Emily Webb
Luis Carvajal-Carmona
Peter Broderick
Zoe Kemp
Sarah Spain
Steven Penegar
Ian Chandler
Maggie Gorman
Wendy Wood
Ella Barclay
Steven Lubbe
Lynn Martin
Gabrielle Sellick
Emma Jaeger
Richard Hubner
Ruth Wild
Andrew Rowan
Sarah Fielding
Kimberley Howarth
Andrew Silver
Wendy Atkin
Kenneth Muir
Richard Logan
David Kerr
Elaine Johnstone
Oliver Sieber
Richard Gray
Huw Thomas
Julian Peto
Jean-Baptiste Cazier
Richard Houlston
Nature Genetics, 2007, 39 : 984 - 988
[16] A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21
Tomlinson, Ian
Webb, Emily
Carvajal-Carmona, Luis
Broderick, Peter
Kemp, Zoe
Spain, Sarah
Penegar, Steven
Chandler, Ian
Gorman, Maggie
Wood, Wendy
Barclay, Ella
Lubbe, Steven
Martin, Lynn
Sellick, Gabrielle
Jaeger, Emma
Hubner, Richard
Wild, Ruth
Rowan, Andrew
Fielding, Sarah
Howarth, Kimberley
Silver, Andrew
Atkin, Wendy
Muir, Kenneth
Logan, Richard
Kerr, David
Johnstone, Elaine
Sieber, Oliver
Gray, Richard
Thomas, Huw
Peto, Julian
Cazier, Baptiste
Houlston, Richard
NATURE GENETICS, 2007, 39 (08) : 984 - 988
[17] A genome-wide association study of upper aerodigestive tract cancers identifies 4q21 4q23, and 12q24 as susceptibility loci
Mckay, James D.
Truong, Therese
Lathrop, Mark
Brennan, Paul
CANCER RESEARCH, 2010, 70
[18] A Genome-Wide Association Study Identifies a Locus for Nonsyndromic Cleft Lip with or without Cleft Palate on 8q24
Grant, Struan F. A.
Wang, Kai
Zhang, Haitao
Glaberson, Wendy
Annaiah, Kiran
Kim, Cecilia E.
Bradfield, Jonathan P.
Glessner, Joseph T.
Thomas, Kelly A.
Garris, Maria
Frackelton, Edward C.
Otieno, F. George
Chiavacci, Rosetta M.
Nah, Hyun-Duck
Kirschner, Richard E.
Hakonarson, Hakon
JOURNAL OF PEDIATRICS, 2009, 155 (06): : 909 - 913
[19] A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1
Lemire, Mathieu
Qu, Conghui
Loo, Lenora W. M.
Zaidi, Syed H. E.
Wang, Hansong
Berndt, Sonja I.
Bezieau, Stephane
Brenner, Hermann
Campbell, Peter T.
Chan, Andrew T.
Chang-Claude, Jenny
Du, Mengmeng
Edlund, Christopher K.
Gallinger, Steven
Haile, Robert W.
Harrison, Tabitha A.
Hoffmeister, Michael
Hopper, John L.
Hou, Lifang
Hsu, Li
Jacobs, Eric J.
Jenkins, Mark A.
Jeon, Jihyoun
Kuery, Sebastien
Li, Li
Lindor, Noralane M.
Newcomb, Polly A.
Potter, John D.
Rennert, Gad
Rudolph, Anja
Schoen, Robert E.
Schumacher, Fredrick R.
Seminara, Daniela
Severi, Gianluca
Slattery, Martha L.
White, Emily
Woods, Michael O.
Cotterchio, Michelle
Le Marchand, Loic
Casey, Graham
Gruber, Stephen B.
Peters, Ulrike
Hudson, Thomas J.
HUMAN GENETICS, 2015, 134 (11-12) : 1249 - 1262
[20] A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1
Mathieu Lemire
Conghui Qu
Lenora W. M. Loo
Syed H. E. Zaidi
Hansong Wang
Sonja I. Berndt
Stéphane Bézieau
Hermann Brenner
Peter T. Campbell
Andrew T. Chan
Jenny Chang-Claude
Mengmeng Du
Christopher K. Edlund
Steven Gallinger
Robert W. Haile
Tabitha A. Harrison
Michael Hoffmeister
John L. Hopper
Lifang Hou
Li Hsu
Eric J. Jacobs
Mark A. Jenkins
Jihyoun Jeon
Sébastien Küry
Li Li
Noralane M. Lindor
Polly A. Newcomb
John D. Potter
Gad Rennert
Anja Rudolph
Robert E. Schoen
Fredrick R. Schumacher
Daniela Seminara
Gianluca Severi
Martha L. Slattery
Emily White
Michael O. Woods
Michelle Cotterchio
Loïc Le Marchand
Graham Casey
Stephen B. Gruber
Ulrike Peters
Thomas J. Hudson
Human Genetics, 2015, 134 : 1249 - 1262

← 1 2 3 4 5 →