Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33

被引：303

作者：

Houlston, Richard S. ^{[1
]}

Cheadle, Jeremy ^{[2
]}

Dobbins, Sara E. ^{[1
]}

Tenesa, Albert ^{[3
,4
]}

Jones, Angela M. ^{[5
]}

Howarth, Kimberley ^{[5
]}

Spain, Sarah L. ^{[5
]}

Broderick, Peter ^{[1
]}

Domingo, Enric ^{[5
]}

Farrington, Susan ^{[3
,4
]}

Prendergast, James G. D. ^{[3
,4
]}

Pittman, Alan M. ^{[1
]}

Theodoratou, Evi ^{[3
,4
]}

Smith, Christopher G. ^{[2
]}

Olver, Bianca ^{[1
]}

Walther, Axel ^{[5
]}

Barnetson, Rebecca A. ^{[3
,4
]}

Churchman, Michael ^{[5
]}

Jaeger, Emma E. M. ^{[5
]}

Penegar, Steven ^{[1
]}

Barclay, Ella ^{[5
]}

Martin, Lynn ^{[5
]}

Gorman, Maggie ^{[5
]}

Mager, Rachel ^{[6
]}

Johnstone, Elaine ^{[6
]}

Midgley, Rachel ^{[6
]}

Niittymaki, Iina ^{[7
]}

Tuupanen, Sari ^{[7
]}

Colley, James ^{[2
]}

Idziaszczyk, Shelley ^{[2
]}

Thomas, Huw J. W. ^{[8
]}

Lucassen, Anneke M. ^{[9
]}

Evans, D. Gareth R. ^{[10
]}

Maher, Eamonn R. ^{[11
,12
]}

Maughan, Timothy ^{[13
]}

Dimas, Antigone ^{[5
,14
]}

Dermitzakis, Emmanouil ^{[14
]}

Cazier, Jean-Baptiste ^{[5
]}

Aaltonen, Lauri A. ^{[7
]}

Pharoah, Paul ^{[15
]}

Kerr, David J. ^{[6
,16
]}

Carvajal-Carmona, Luis G. ^{[5
]}

Campbell, Harry

Dunlop, Malcolm G. ^{[3
,4
]}

Tomlinson, Ian P. M. ^{[5
]}

机构：

[1] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England

[2] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff, S Glam, Wales

[3] Univ Edinburgh, Inst Genet & Mol Med, Colon Canc Genet Grp, Edinburgh, Midlothian, Scotland

[4] MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland

[5] Wellcome Trust Ctr Human Genet, Oxford, England

[6] Univ Oxford, Radcliffe Infirm, Dept Clin Pharmacol, Oxford OX2 6HE, England

[7] Univ Helsinki, Biomedicum Helsinki, Genome Scale Biol Res Program, Dept Med Genet, Helsinki, Finland

[8] St Marks Hosp, Colorectal Canc Unit, Harrow, Middx, England

[9] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England

[10] St Marys Hosp, Manchester M13 0JH, Lancs, England

[11] Brigham & Womens Hosp, W Midlands Reg Genet Serv, Birmingham, W Midlands, England

[12] Univ Birmingham, Dept Med & Mol Genet, Sch Clin & Expt Med, Inst Biomed Res, Birmingham, W Midlands, England

[13] Cardiff Univ, Sch Med, Dept Oncol & Palliat Care, Cardiff, S Glam, Wales

[14] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland

[15] Univ Cambridge, Canc Res UK Labs, Strangeways Res Lab, Dept Oncol, Cambridge, England

[16] Qatar Fdn, Sidra Med & Res Ctr, Doha, Qatar

来源：

NATURE GENETICS | 2010年 / 42卷 / 11期

基金：

英国医学研究理事会; 芬兰科学院;

关键词：

RISK; GENETICS; DISEASE; VARIANT; SCAN;

D O I：

10.1038/ng.670

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 x 10(-10) and rs6687758, OR = 1.09, P = 2.27 x 10(-9)), 3q26.2 (rs10936599, OR = 0.93, P = 3.39 x 10(-8)), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 x 10(-10) and rs7136702, OR = 1.06, P = 4.02 x 10(-8)) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 x 10(-10)). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.

引用

页码：973 / U89

页数：7

共 14 条

[1] A genome-wide association study of global gene expression [J].

Dixon, Anna L. ;

Liang, Liming ;

Moffatt, Miriam F. ;

Chen, Wei ;

Heath, Simon ;

Wong, Kenny C. C. ;

Taylor, Jenny ;

Burnett, Edward ;

Gut, Ivo ;

Farrall, Martin ;

Lathrop, G. Mark ;

Abecasis, Goncalo R. ;

Cookson, William O. C. .

NATURE GENETICS, 2007, 39 (10) :1202-1207

[2] A common genetic risk factor for colorectal and prostate cancer [J].

Haiman, Christopher A. ;

Le Marchand, Loic ;

Yamamato, Jennifer ;

Stram, Daniel O. ;

Sheng, Xin ;

Kolonel, Laurence N. ;

Wu, Anna H. ;

Reich, David ;

Henderson, Brian E. .

NATURE GENETICS, 2007, 39 (08) :954-956

[3] Quantifying heterogeneity in a meta-analysis [J].

Higgins, JPT ;

Thompson, SG .

STATISTICS IN MEDICINE, 2002, 21 (11) :1539-1558

[4] Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer [J].

Houlston, Richard S. ;

Webb, Emily ;

Broderick, Peter ;

Pittman, Alan M. ;

Di Bernardo, Maria Chiara ;

Lubbe, Steven ;

Chandler, Ian ;

Vijayakrishnan, Jayaram ;

Sullivan, Kate ;

Penegar, Steven ;

Carvajal-Carmona, Luis ;

Howarth, Kimberley ;

Jaeger, Emma ;

Spain, Sarah L. ;

Walther, Axel ;

Barclay, Ella ;

Martin, Lynn ;

Gorman, Maggie ;

Domingo, Enric ;

Teixeira, Ana S. ;

Kerr, David ;

Cazier, Jean-Baptiste ;

Niittymaki, Iina ;

Tuupanen, Sari ;

Karhu, Auli ;

Aaltonen, Lauri A. ;

Tomlinson, Ian P. M. ;

Farrington, Susan M. ;

Tenesa, Albert ;

Prendergast, James G. D. ;

Barnetson, Rebecca A. ;

Cetnarskyj, Roseanne ;

Porteous, Mary E. ;

Pharoah, Paul D. P. ;

Koessler, Thibaud ;

Hampe, Jochen ;

Buch, Stephan ;

Schafmayer, Clemens ;

Tepel, Jurgen ;

Schreiber, Stefan ;

Voelzke, Henry ;

Chang-Claude, Jenny ;

Hoffmeister, Michael ;

Brenner, Hermann ;

Zanke, Brent W. ;

Montpetit, Alexandre ;

Hudson, Thomas J. ;

Gallinger, Steven ;

Campbell, Harry ;

Dunlop, Malcolm G. .

NATURE GENETICS, 2008, 40 (12) :1426-1435

[5] Genetics of coeliac disease [J].

Houlston, RS ;

Ford, D .

QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, 1996, 89 (10) :737-743

[6]

Johns LE, 2001, AM J GASTROENTEROL, V96, P2992, DOI 10.1111/j.1572-0241.2001.04677.x

[7] Array-CGH analysis of microsatellite-stable, near-diploid bowel cancers and comparison with other types of colorectal carcinoma [J].

Jones, AM ;

Douglas, EJ ;

Halford, SER ;

Fiegler, H ;

Gorman, PA ;

Roylance, RR ;

Carter, NP ;

Tomlinson, IPM .

ONCOGENE, 2005, 24 (01) :118-129

[8]

Petitti Diana B., 1994, Annals of Epidemiology, V4, P115

[9] The influence of birth weight and socioeconomic position on cognitive development: Does the early home and learning environment modify their effects? [J].

Power, C ;

Jefferis, BJMH ;

Manor, O ;

Hertzman, C .

JOURNAL OF PEDIATRICS, 2006, 148 (01) :54-61

[10] The allelic architecture of human disease genes: common disease - common variant ... or not? [J].

Pritchard, JK ;

Cox, NJ .

HUMAN MOLECULAR GENETICS, 2002, 11 (20) :2417-2423

← 1 2 →