Association study of germline variants in CCNB1 and CDK1 with breast cancer susceptibility, progression, and survival among Chinese Han women.
Association study of germline variants in CCNB1 and CDK1 with breast cancer susceptibility, progression, and survival among Chinese Han women.
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CCNB1和CDK1种系变异与中国汉族女性乳腺癌易感性、进展和生存的关联研究
DOI：
10.1371/journal.pone.0084489
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fang WG
中科院分区：
文献类型：
--
作者：
Li Y;Chen YL;Xie YT;Zheng LY;Han JY;Wang H;Tian XX;Fang WG
CCNB 1和CDK 1基因分别编码CyclinB 1和CDK 1蛋白，它们相互作用，参与细胞周期调控、中心体复制和染色体分离。本研究旨在通过单体型分析探讨这两个基因的遗传变异是否可能影响中国汉族人群乳腺癌的易感性、进展和生存率。在1204例病例和1204例年龄匹配的无癌对照中，对这些基因上游2kb至下游2kb的10个tSNPs进行基因分型。根据我们的基因分型数据和这些SNP的连锁不平衡（LD）状态确定单倍型区组。CCNB 1基因rs 2069429和TAGT/TAGT双倍型与BC易感性呈显著相关（OR=2.352，95%CI =1.480-3.737，P=0.013）。此外，rs 164390与Her 2阴性BC相关。对于CDK 1，rs 2448343和rs 1871446在显性模型下与BC风险降低显著相关，单倍型ATATT也是如此。这两个SNP也显示出对BC易感性的剂量依赖性效应。分层关联分析发现，在BMI<23的女性中，携带rs 2448343杂合子或次等位基因纯合子的女性对BC的易感性要低得多。在CDK 1中，三个位置接近的SNP，rs 2448343，rs3213048和rs3213067，与肿瘤的PR状态显著相关：rs 2448343的杂合子与PR阳性肿瘤相关，而rs3213048的次要等位基因纯合子和rs3213067的杂合子与PR阴性BC肿瘤相关。在生存分析中，rs 1871446与隐性模型下的不利无事件生存相关，CDK 1双体型ATATG/ATATG也是如此，其携带rs 1871446的次要等位基因纯合子。我们的研究表明，CCNB 1和CDK 1基因多态性与中国汉族妇女BC的易感性，进展和生存。需要在其他人群中进行进一步的研究作为独立的重复来验证这些结果。
The CCNB1 and CDK1 genes encode the proteins of CyclinB1 and CDK1 respectively, which interact with each other and are involved in cell cycle regulation, centrosome duplication and chromosome segregation. This study aimed to investigate whether the genetic variants in these two genes may affect breast cancer (BC) susceptibility, progression, and survival in Chinese Han population using haplotype-based analysis. A total of ten tSNPs spanning from 2kb upstream to 2kb downstream of these genes were genotyped in 1204 cases and 1204 age-matched cancer-free controls. The haplotype blocks were determined according to our genotyping data and linkage disequilibrium (LD) status of these SNPs. For CCNB1, rs2069429 was significantly associated with increased BC susceptibility under recessive model (OR=2.352, 95%CI=1.480-3.737), so was the diplotype TAGT/TAGT (OR=1.947 95%CI=1.154-3.284, P=0.013). In addition, rs164390 was associated with Her2-negative BC. For CDK1, rs2448343 and rs1871446 were significantly associated with decreased BC risk under dominant models, so was the haplotype ATATT. These two SNPs also showed a dose-dependent effect on BC susceptibility. Using stratified association analysis, we found that women with the heterozygotes or minor allele homozygotes of rs2448343 had much less BC susceptibility among women with BMI<23. In CDK1, three closely located SNPs, rs2448343, rs3213048 and rs3213067, were significantly associated with tumor’s PR status: the heterozygotes of rs2448343 were associated with PR-positive tumors, while the minor allele homozygotes of rs3213048 and heterozygotes of rs3213067 were associated with PR-negative BC tumors. In survival analysis, rs1871446 was associated with unfavorable event-free survival under recessive model, so was the CDK1 diplotype ATATG/ATATG, which carried the minor allele homozygote of rs1871446. Our study indicates that genetic polymorphisms of CCNB1 and CDK1 are related to BC susceptibility, progression, and survival in Chinese Han women. Further studies need to be performed in other populations as an independent replication to verify these results.
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影响因子：
9.2
作者：
Hagting, A;Jackman, M;Pines, J
通讯作者：
Pines, J
DOI：
10.1073/pnas.94.2.502
发表时间：
1997-01-21
影响因子：
11.1
作者：
Li, J;Meyer, AN;Donoghue, DJ
通讯作者：
Donoghue, DJ
影响因子：
3.5
作者：
Kang, Huafeng;Dai, Zhijun;Wang, Xijing
通讯作者：
Wang, Xijing
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：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D