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IR@PKUHSC  > 北京大学临床肿瘤学院  > 期刊论文
学科主题: 临床医学
题名:
Association Study of Germline Variants in CCNB1 and CDK1 with Breast Cancer Susceptibility, Progression, and Survival among Chinese Han Women
作者: Li, Yan1; Chen, Yi-Lin1; Xie, Yun-Tao2; Zheng, Li-Yuan1; Han, Ji-Yuan1; Wang, Hui1; Tian, Xin-Xia1; Fang, Wei-Gang1
刊名: PLOS ONE
发表日期: 2013-12-27
DOI: 10.1371/journal.pone.0084489
卷: 8, 期:12
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: CELL LUNG-CANCER ; GENOME-WIDE ASSOCIATION ; GENETIC POLYMORPHISMS ; MESSENGER-RNA ; CYCLIN B1 ; RISK ; POPULATION ; PHOSPHORYLATION ; LOCALIZATION ; MICROARRAY
英文摘要:

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.

语种: 英语
所属项目编号: 81171961 ; 20110001110060
项目资助者: National Natural Science Foundation of China ; Ministry of Education of China
WOS记录号: WOS:000329117900099
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54449
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci,Minist Educ, Dept Pathol,Key Lab Carcinogenesis & Translat Res, Beijing 100871, Peoples R China
2.Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Breast Ctr, Beijing 100871, Peoples R China

Recommended Citation:
Li, Yan,Chen, Yi-Lin,Xie, Yun-Tao,et al. Association Study of Germline Variants in CCNB1 and CDK1 with Breast Cancer Susceptibility, Progression, and Survival among Chinese Han Women[J]. PLOS ONE,2013,8(12).
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