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

被引：473

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

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