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Association Study of Germline Variants in CCNB1 and CDK1 with Breast Cancer Susceptibility, Progression, and Survival among Chinese Han Women
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
2013-12-27
DOI10.1371/journal.pone.0084489
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
WOS记录号WOS:000329117900099
引用统计
被引频次:1[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54449
专题北京大学临床肿瘤学院
北京大学医学部管理机构_主任办公室党委办公室
北京大学基础医学院
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
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GB/T 7714
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).
APA Li, Yan.,Chen, Yi-Lin.,Xie, Yun-Tao.,Zheng, Li-Yuan.,Han, Ji-Yuan.,...&Fang, Wei-Gang.(2013).Association Study of Germline Variants in CCNB1 and CDK1 with Breast Cancer Susceptibility, Progression, and Survival among Chinese Han Women.PLOS ONE,8(12).
MLA Li, Yan,et al."Association Study of Germline Variants in CCNB1 and CDK1 with Breast Cancer Susceptibility, Progression, and Survival among Chinese Han Women".PLOS ONE 8.12(2013).
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