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

被引：193

作者：

Dunlop, Malcolm G. ^{[1
,2
]}

Dobbins, Sara E. ^{[3
]}

Farrington, Susan Mary ^{[1
,2
]}

Jones, Angela M. ^{[4
]}

Palles, Claire ^{[4
]}

Whiffin, Nicola ^{[3
]}

Tenesa, Albert ^{[1
,2
]}

Spain, Sarah ^{[4
]}

Broderick, Peter ^{[3
]}

Ooi, Li-Yin ^{[1
,2
]}

Domingo, Enric ^{[4
]}

Smillie, Claire ^{[1
,2
]}

Henrion, Marc ^{[3
]}

Frampton, Matthew ^{[3
]}

Martin, Lynn ^{[4
]}

Grimes, Graeme ^{[1
,2
]}

Gorman, Maggie ^{[4
]}

Semple, Colin ^{[1
,2
]}

Ma, Yusanne P. ^{[3
]}

Barclay, Ella ^{[4
]}

Prendergast, James ^{[1
,2
]}

Cazier, Jean-Baptiste ^{[4
]}

Olver, Bianca ^{[3
]}

Penegar, Steven ^{[3
]}

Lubbe, Steven ^{[3
]}

Chander, Ian ^{[5
]}

Carvajal-Carmona, Luis G. ^{[4
]}

Ballereau, Stephane ^{[1
,2
]}

Lloyd, Amy ^{[3
]}

Vijayakrishnan, Jayaram ^{[3
]}

Zgaga, Lina ^{[1
,2
]}

Rudan, Igor

Theodoratou, Evropi

Starr, John M. ^{[6
]}

Deary, Ian ^{[6
]}

Kirac, Iva ^{[7
]}

Kovacevic, Dujo ^{[8
]}

Aaltonen, Lauri A. ^{[9
]}

Renkonen-Sinisalo, Laura ^{[10
]}

Mecklin, Jukka-Pekka ^{[11
]}

Matsuda, Koichi ^{[12
]}

Nakamura, Yusuke ^{[12
]}

Okada, Yukinori ^{[13
]}

Gallinger, Steven ^{[14
]}

Duggan, David J. ^{[15
]}

Conti, David ^{[16
]}

Newcomb, Polly ^{[17
]}

Hopper, John ^{[18
]}

Jenkins, Mark A. ^{[18
]}

Schumacher, Fredrick ^{[16
]}

机构：

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

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

[3] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England

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

[5] Royal Devon & Exeter Hosp, Dept Histopathol, Exeter EX2 5DW, Devon, England

[6] Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[7] Univ Hosp Tumors, Univ Hosp Ctr Sestre Milosrdnice, Dept Surg Oncol, Zagreb, Croatia

[8] Univ Hosp Ctr Sestre Milosrdnice, Dept Surg, Zagreb, Croatia

[9] Univ Helsinki, Dept Med Genet, Genome Scale Biol Res Program, Biomed Helsinki, Helsinki, Finland

[10] Univ Helsinki, Cent Hosp, Dept Surg, Helsinki, Finland

[11] Univ Eastern Finland, Jyvaskyla Cent Hosp, Jyvaskyla, Finland

[12] Univ Tokyo, Inst Med Sci, Mol Med Lab, Tokyo, Japan

[13] RIKEN, Inst Phys & Chem Res, Ctr Genom Med, Lab Stat Anal, Kanagawa, Japan

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

[15] Translat Genom Res Inst TGen, Phoenix, AZ USA

[16] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA

[17] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA

[18] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[19] Univ Cambridge, Dept Oncol, Cambridge, England

[20] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

[21] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[22] Cardiff Univ, Sch Med, Inst Canc & Genet, Cardiff, S Glam, Wales

[23] Univ Oxford, Radcliffe Infirm, Dept Oncol, Oxford OX2 6HE, England

[24] Comprehens Biomed Res Ctr, Oxford Natl Inst Hlth Res NIHR, Oxford, England

来源：

NATURE GENETICS | 2012年 / 44卷 / 07期

基金：

英国生物技术与生命科学研究理事会; 美国国家卫生研究院; 英国惠康基金; 芬兰科学院; 英国工程与自然科学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; X-CHROMOSOME INACTIVATION; SUSCEPTIBILITY LOCI; MICROSATELLITE INSTABILITY; GENE-EXPRESSION; METAANALYSIS; MUTATIONS; VARIANTS;

D O I：

10.1038/ng.2293

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 x 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 x 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.

引用

页码：770 / U197

页数：9

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