Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
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东亚的大规模遗传研究确定了与结直肠癌风险相关的六个新基因座。
DOI：
10.1038/ng.2985
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发表时间：
2014-06
期刊：
影响因子：
30.8
通讯作者：
Zheng, Wei
中科院分区：
文献类型：
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作者：
Zhang, Ben;Jia, Wei-Hua;Matsuda, Koichi;Kweon, Sun-Seog;Matsuo, Keitaro;Xiang, Yong-Bing;Shin, Aesun;Jee, Sun Ha;Kim, Dong-Hyun;Cai, Qiuyin;Long, Jirong;Shi, Jiajun;Wen, Wanqing;Yang, Gong;Zhang, Yanfeng;Li, Chun;Li, Bingshan;Guo, Yan;Ren, Zefang;Ji, Bu-Tian;Pan, Zhi-Zhong;Takahashi, Atsushi;Shin, Min-Ho;Matsuda, Fumihiko;Gao, Yu-Tang;Oh, Jae Hwan;Kim, Soriul;Ahn, Yoon-Ok;Chan, Andrew T.;Chang-Claude, Jenny;Slattery, Martha L.;Gruber, Stephen B.;Schumacher, Fredrick R.;Stenzel, Stephanie L.;Casey, Graham;Kim, Hyeong-Rok;Jeong, Jin-Young;Park, Ji Won;Li, Hong-Lan;Hosono, Satoyo;Cho, Sang-Hee;Kubo, Michiaki;Shu, Xiao-Ou;Zeng, Yi-Xin;Zheng, Wei
已知的基因位点仅能解释结直肠癌（CRC）家族相对风险的一小部分。我们在东亚人群中进行了一项最大规模的全基因组关联研究，涉及14963例结直肠癌病例和31945例对照，在10q22.3、10q25.2、11q12.2、12p13.31、17p13.3和19q13.2位点鉴定出6个与结直肠癌风险相关的新位点（P = 3.42×10⁻⁸至9.22×10⁻²¹）。其中两个位点定位在在结直肠肿瘤发生中已确定作用的基因（TCF7L2和TGFB1）上。另外四个位点位于参与转录调控（ZMIZ1）、基因组维持（FEN1）、脂肪酸代谢（FADS1和FADS2）、癌细胞运动和转移（CD9）以及细胞生长和分化（NXN）的基因内部或附近。我们还发现了在8q24.11、10q21.1和10q24.2位点接近全基因组显著水平的与结直肠癌风险相关的另外三个位点的提示性证据。此外，我们重复验证了22个先前报道的结直肠癌位点。我们的研究为结直肠癌的遗传基础提供了见解，并提示了新的生物学途径。
Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted the largest genome-wide association study in East Asians with 14,963 CRC cases and 31,945 controls and identified six new loci associated with CRC risk (P = 3.42 × 10−8 to 9.22 × 10−21) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcription regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9) and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC loci. Our study provides insights into the genetic basis of CRC and suggests new biological pathways.
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影响因子：
56.9
作者：
Howe, JR;Roth, S;Aaltonen, LA
通讯作者：
Aaltonen, LA
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
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影响因子：
30.8
作者：
通讯作者：
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
30.8
作者：
Dunlop MG;Dobbins SE;Farrington SM;Jones AM;Palles C;Whiffin N;Tenesa A;Spain S;Broderick P;Ooi LY;Domingo E;Smillie C;Henrion M;Frampton M;Martin L;Grimes G;Gorman M;Semple C;Ma YP;Barclay E;Prendergast J;Cazier JB;Olver B;Penegar S;Lubbe S;Chander I;Carvajal-Carmona LG;Ballereau S;Lloyd A;Vijayakrishnan J;Zgaga L;Rudan I;Theodoratou E;Colorectal Tumour Gene Identification (CORGI) Consortium;Starr JM;Deary I;Kirac I;Kovacević D;Aaltonen LA;Renkonen-Sinisalo L;Mecklin JP;Matsuda K;Nakamura Y;Okada Y;Gallinger S;Duggan DJ;Conti D;Newcomb P;Hopper J;Jenkins MA;Schumacher F;Casey G;Easton D;Shah M;Pharoah P;Lindblom A;Liu T;Swedish Low-Risk Colorectal Cancer Study Group;Smith CG;West H;Cheadle JP;COIN Collaborative Group;Midgley R;Kerr DJ;Campbell H;Tomlinson IP;Houlston RS
通讯作者：
Houlston RS