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

被引：472

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

[31] A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3
Tomlinson, Ian P. M.
Webb, Emily
Carvajal-Carmona, Luis
Broderick, Peter
Howarth, Kimberley
Pittman, Alan M.
Spain, Sarah
Lubbe, Steven
Walther, Axel
Sullivan, Kate
Jaeger, Emma
Fielding, Sarah
Rowan, Andrew
Vijayakrishnan, Jayaram
Domingo, Enric
Chandler, Ian
Kemp, Zoe
Qureshi, Mobshra
Farrington, Susan M.
Tenesa, Albert
Prendergast, James G. D.
Barnetson, Rebecca A.
Penegar, Steven
Barclay, Ella
Wood, Wendy
Martin, Lynn
Gorman, Maggie
Thomas, Huw
Peto, Julian
Bishop, D. Timothy
Gray, Richard
Maher, Eamonn R.
Lucassen, Anneke
Kerr, David
Evans, D. Gareth R.
Schafmayer, Clemens
Buch, Stephan
Voelzke, Henry
Hampe, Jochen
Schreiber, Stefan
John, Ulrich
Koessler, Thibaud
Pharoah, Paul
van Wezel, Tom
Morreau, Hans
Wijnen, Juul T.
Hopper, John L.
Southey, Melissa C.
Giles, Graham G.
Severi, Gianluca
NATURE GENETICS, 2008, 40 (05) : 623 - 630
[32] Erratum: Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2
Thorsten Thye
Fredrik O Vannberg
Sunny H Wong
Ellis Owusu-Dabo
Ivy Osei
John Gyapong
Giorgio Sirugo
Fatou Sisay-Joof
Anthony Enimil
Margaret A Chinbuah
Sian Floyd
David K Warndorff
Lifted Sichali
Simon Malema
Amelia C Crampin
Bagrey Ngwira
Yik Y Teo
Kerrin Small
Kirk Rockett
Dominic Kwiatkowski
Paul E Fine
Philip C Hill
Melanie Newport
Christian Lienhardt
Richard A Adegbola
Tumani Corrah
Andreas Ziegler
Andrew P Morris
Christian G Meyer
Rolf D Horstmann
Adrian V S Hill
Nature Genetics, 2011, 43 : 1040 - 1040
[33] Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21
Christopher A Haiman
Gary K Chen
William J Blot
Sara S Strom
Sonja I Berndt
Rick A Kittles
Benjamin A Rybicki
William B Isaacs
Sue A Ingles
Janet L Stanford
W Ryan Diver
John S Witte
Ann W Hsing
Barbara Nemesure
Timothy R Rebbeck
Kathleen A Cooney
Jianfeng Xu
Adam S Kibel
Jennifer J Hu
Esther M John
Serigne M Gueye
Stephen Watya
Lisa B Signorello
Richard B Hayes
Zhaoming Wang
Edward Yeboah
Yao Tettey
Qiuyin Cai
Suzanne Kolb
Elaine A Ostrander
Charnita Zeigler-Johnson
Yuko Yamamura
Christine Neslund-Dudas
Jennifer Haslag-Minoff
William Wu
Venetta Thomas
Glenn O Allen
Adam Murphy
Bao-Li Chang
S Lilly Zheng
M Cristina Leske
Suh-Yuh Wu
Anna M Ray
Anselm J M Hennis
Michael J Thun
John Carpten
Graham Casey
Erin N Carter
Edder R Duarte
Lucy Y Xia
Nature Genetics, 2011, 43 : 570 - 573
[34] Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21
Haiman, Christopher A.
Chen, Gary K.
Blot, William J.
Strom, Sara S.
Berndt, Sonja I.
Kittles, Rick A.
Rybicki, Benjamin A.
Isaacs, William B.
Ingles, Sue A.
Stanford, Janet L.
Diver, W. Ryan
Witte, John S.
Hsing, Ann W.
Nemesure, Barbara
Rebbeck, Timothy R.
Cooney, Kathleen A.
Xu, Jianfeng
Kibel, Adam S.
Hu, Jennifer J.
John, Esther M.
Gueye, Serigne M.
Watya, Stephen
Signorello, Lisa B.
Hayes, Richard B.
Wang, Zhaoming
Yeboah, Edward
Tettey, Yao
Cai, Qiuyin
Kolb, Suzanne
Ostrander, Elaine A.
Zeigler-Johnson, Charnita
Yamamura, Yuko
Neslund-Dudas, Christine
Haslag-Minoff, Jennifer
Wu, William
Thomas, Venetta
Allen, Glenn O.
Murphy, Adam
Chang, Bao-Li
Zheng, S. Lilly
Leske, M. Cristina
Wu, Suh-Yuh
Ray, Anna M.
Hennis, Anselm J. M.
Thun, Michael J.
Carpten, John
Casey, Graham
Carter, Erin N.
Duarte, Edder R.
Xia, Lucy Y.
NATURE GENETICS, 2011, 43 (06) : 570 - U103
[35] Pooled analysis confirms association between 8q24 locus and colorectal adenoma risk
Berndt, Sonja
Potter, John
Hazra, Aditi
Yeager, Meredith
Makar, Karen
Welch, Robert
Cross, Amanda
Huang, Wen-Yi
Thomas, Gilles
Chanock, Stephen
Peters, Ulrike
Hunter, David
Hayes, Richard
CANCER RESEARCH, 2008, 68 (09)
[36] Association of 8q23-24 region (8q23.3 loci and 8q24.21 loci) with susceptibility to colorectal cancer: a systematic and updated meta-analysis
Li, Linlin
Lv, Li
Liang, Yuan
Shen, Xiaoyu
Zhou, Shishi
Zhu, Jia
Ma, Rui
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2015, 8 (11): : 21001 - +
[37] Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21
Tanikawa, Chizu
Kamatani, Yoichiro
Toyoshima, Osamu
Sakamoto, Hiromi
Ito, Hidemi
Takahashi, Atsushi
Momozawa, Yukihide
Hirata, Makoto
Fuse, Nobuo
Takai-Igarashi, Takako
Shimizu, Atsushi
Sasaki, Makoto
Yamaji, Taiki
Sawada, Norie
Iwasaki, Motoki
Tsugane, Shoichiro
Naito, Mariko
Hishida, Asahi
Wakai, Kenji
Furusyo, Norihiro
Murakami, Yoshinori
Nakamura, Yusuke
Imoto, Issei
Inazawa, Johji
Oze, Isao
Sato, Naomi
Tanioka, Fumihiko
Sugimura, Haruhiko
Hirose, Hiroshi
Yoshida, Teruhiko
Matsuo, Keitaro
Kubo, Michiaki
Matsuda, Koichi
CANCER SCIENCE, 2018, 109 (12): : 4015 - 4024
[38] Genome-wide association study identifies two new susceptibility loci for colorectal cancer at 5q23.3 and 17q12 in Han Chinese
Jiang, Kewei
Sun, Yimin
Wang, Cheng
Ji, Jiafu
Li, Yaoping
Ye, Yingjiang
Lv, Liang
Guo, Yong
Guo, Sutang
Li, Hai
Zhang, Lianhai
Zhou, Yanbing
Jiang, Bo
Ren, Yonghong
Xu, Youchun
Yang, Xiongfei
Liu, Hongxia
Wang, Yirui
Shen, Zhanlong
Qin, Wenyan
Guo, Peng
Jiang, Yuyang
Hu, Zhibin
Shen, Hongbing
Cheng, Jing
Yang, Yinxue
Wang, Shan
ONCOTARGET, 2015, 6 (37) : 40327 - 40336
[39] Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction
Bezzina, Connie R.
Pazoki, Raha
Bardai, Abdennasser
Marsman, Roos F.
de Jong, Jonas S. S. G.
Blom, Marieke T.
Scicluna, Brendon P.
Jukema, J. Wouter
Bindraban, Navin R.
Lichtner, Peter
Pfeufer, Arne
Bishopric, Nanette H.
Roden, Dan M.
Meitinger, Thomas
Chugh, Sumeet S.
Myerburg, Robert J.
Jouven, Xavier
Kaab, Stefan
Dekker, Lukas R. C.
Tan, Hanno L.
Tanck, Michael W. T.
Wilde, Arthur A. M.
NATURE GENETICS, 2010, 42 (08) : 688 - U64
[40] Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction
Connie R Bezzina
Raha Pazoki
Abdennasser Bardai
Roos F Marsman
Jonas S S G de Jong
Marieke T Blom
Brendon P Scicluna
J Wouter Jukema
Navin R Bindraban
Peter Lichtner
Arne Pfeufer
Nanette H Bishopric
Dan M Roden
Thomas Meitinger
Sumeet S Chugh
Robert J Myerburg
Xavier Jouven
Stefan Kääb
Lukas R C Dekker
Hanno L Tan
Michael W T Tanck
Arthur A M Wilde
Nature Genetics, 2010, 42 : 688 - 691

← 1 2 3 4 5 →